Impact of injection sites on clinical pharmacokinetics of subcutaneously administered peptides and proteins
For most approved subcutaneously (SC) administered drug products in the US, the recommended injection sites (i.e., abdomen, thigh, and upper arm) are usually based on experience from phase 3 trials. Relative bioavailability data directly comparing the pharmacokinetics (PK) of different SC injection...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Zou, Peng [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2021transfer abstract |
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| Umfang: |
12 |
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| Übergeordnetes Werk: |
Enthalten in: 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up - Moschini, M. ELSEVIER, 2015, official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems, New York, NY [u.a.] |
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| Übergeordnetes Werk: |
volume:336 ; year:2021 ; day:10 ; month:08 ; pages:310-321 ; extent:12 |
| Links: |
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| DOI / URN: |
10.1016/j.jconrel.2021.06.038 |
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ELV054897564 |
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| 520 | |a For most approved subcutaneously (SC) administered drug products in the US, the recommended injection sites (i.e., abdomen, thigh, and upper arm) are usually based on experience from phase 3 trials. Relative bioavailability data directly comparing the pharmacokinetics (PK) of different SC injection sites are often not available and the underlying mechanisms that may affect SC absorption have not been systematically investigated. In this study, we surveyed clinical PK data (AUC, Cmax, and Tmax) for SC administered drug products including therapeutic proteins and peptides based on literature and FDA database. The PK data after abdominal injection was used as a reference to determine the relative bioavailability of SC injections to the arm and thigh. The survey retrieved 19 immunoglobulin G (IgGs), 18 peptides/small proteins (molecular weight < 16 kDa), and 8 non-IgG proteins that had available clinical PK data from multiple SC injection sites. Among these, 5 (26%) IgGs, 9 (50%) peptides/small proteins, and 3 (38%) non-IgG proteins, exhibited injection site-dependent PK (i.e. PK differed by injection sites). Correlation analyses revealed that the PK of peptides/small proteins undergoing rapid SC absorption (Tmax ≤ 2 h), elimination (CL/F ≥ 39 L/h) or low plasma protein binding were more sensitive to injection sites. Similarly, non-IgG proteins (molecular weight ≥ 16 kDa) with high CL/F and low Tmax are associated with high risk of injection site-dependent SC absorption. IgGs with T1/2 < 15 days or Tmax < 5 days are more likely to show injection site-dependent SC absorption. Positive charge of the drug molecule (isoelectric point ≥8) may reduce SC absorption from all three injection sites but is not associated with high risk of injection site-dependent SC absorption. In summary, the results suggested that regional differences in pre-systemic catabolism and local SC blood flow potentially contribute injection site-dependent SC absorption of peptides/small proteins while local lymphatic flow and FcRn binding likely contribute to site-dependent SC absorption of IgGs. | ||
| 520 | |a For most approved subcutaneously (SC) administered drug products in the US, the recommended injection sites (i.e., abdomen, thigh, and upper arm) are usually based on experience from phase 3 trials. Relative bioavailability data directly comparing the pharmacokinetics (PK) of different SC injection sites are often not available and the underlying mechanisms that may affect SC absorption have not been systematically investigated. In this study, we surveyed clinical PK data (AUC, Cmax, and Tmax) for SC administered drug products including therapeutic proteins and peptides based on literature and FDA database. The PK data after abdominal injection was used as a reference to determine the relative bioavailability of SC injections to the arm and thigh. The survey retrieved 19 immunoglobulin G (IgGs), 18 peptides/small proteins (molecular weight < 16 kDa), and 8 non-IgG proteins that had available clinical PK data from multiple SC injection sites. Among these, 5 (26%) IgGs, 9 (50%) peptides/small proteins, and 3 (38%) non-IgG proteins, exhibited injection site-dependent PK (i.e. PK differed by injection sites). Correlation analyses revealed that the PK of peptides/small proteins undergoing rapid SC absorption (Tmax ≤ 2 h), elimination (CL/F ≥ 39 L/h) or low plasma protein binding were more sensitive to injection sites. Similarly, non-IgG proteins (molecular weight ≥ 16 kDa) with high CL/F and low Tmax are associated with high risk of injection site-dependent SC absorption. IgGs with T1/2 < 15 days or Tmax < 5 days are more likely to show injection site-dependent SC absorption. Positive charge of the drug molecule (isoelectric point ≥8) may reduce SC absorption from all three injection sites but is not associated with high risk of injection site-dependent SC absorption. In summary, the results suggested that regional differences in pre-systemic catabolism and local SC blood flow potentially contribute injection site-dependent SC absorption of peptides/small proteins while local lymphatic flow and FcRn binding likely contribute to site-dependent SC absorption of IgGs. | ||
| 700 | 1 | |a Wang, Fuyuan |4 oth | |
| 700 | 1 | |a Wang, Jie |4 oth | |
| 700 | 1 | |a Lu, Yanhui |4 oth | |
| 700 | 1 | |a Tran, Doanh |4 oth | |
| 700 | 1 | |a Seo, Shirley K. |4 oth | |
| 773 | 0 | 8 | |i Enthalten in |n Elsevier |a Moschini, M. ELSEVIER |t 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up |d 2015 |d official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems |g New York, NY [u.a.] |w (DE-627)ELV012920894 |
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10.1016/j.jconrel.2021.06.038 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001481.pica (DE-627)ELV054897564 (ELSEVIER)S0168-3659(21)00336-9 DE-627 ger DE-627 rakwb eng 610 VZ 670 VZ 35.80 bkl Zou, Peng verfasserin aut Impact of injection sites on clinical pharmacokinetics of subcutaneously administered peptides and proteins 2021transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier For most approved subcutaneously (SC) administered drug products in the US, the recommended injection sites (i.e., abdomen, thigh, and upper arm) are usually based on experience from phase 3 trials. Relative bioavailability data directly comparing the pharmacokinetics (PK) of different SC injection sites are often not available and the underlying mechanisms that may affect SC absorption have not been systematically investigated. In this study, we surveyed clinical PK data (AUC, Cmax, and Tmax) for SC administered drug products including therapeutic proteins and peptides based on literature and FDA database. The PK data after abdominal injection was used as a reference to determine the relative bioavailability of SC injections to the arm and thigh. The survey retrieved 19 immunoglobulin G (IgGs), 18 peptides/small proteins (molecular weight < 16 kDa), and 8 non-IgG proteins that had available clinical PK data from multiple SC injection sites. Among these, 5 (26%) IgGs, 9 (50%) peptides/small proteins, and 3 (38%) non-IgG proteins, exhibited injection site-dependent PK (i.e. PK differed by injection sites). Correlation analyses revealed that the PK of peptides/small proteins undergoing rapid SC absorption (Tmax ≤ 2 h), elimination (CL/F ≥ 39 L/h) or low plasma protein binding were more sensitive to injection sites. Similarly, non-IgG proteins (molecular weight ≥ 16 kDa) with high CL/F and low Tmax are associated with high risk of injection site-dependent SC absorption. IgGs with T1/2 < 15 days or Tmax < 5 days are more likely to show injection site-dependent SC absorption. Positive charge of the drug molecule (isoelectric point ≥8) may reduce SC absorption from all three injection sites but is not associated with high risk of injection site-dependent SC absorption. In summary, the results suggested that regional differences in pre-systemic catabolism and local SC blood flow potentially contribute injection site-dependent SC absorption of peptides/small proteins while local lymphatic flow and FcRn binding likely contribute to site-dependent SC absorption of IgGs. For most approved subcutaneously (SC) administered drug products in the US, the recommended injection sites (i.e., abdomen, thigh, and upper arm) are usually based on experience from phase 3 trials. Relative bioavailability data directly comparing the pharmacokinetics (PK) of different SC injection sites are often not available and the underlying mechanisms that may affect SC absorption have not been systematically investigated. In this study, we surveyed clinical PK data (AUC, Cmax, and Tmax) for SC administered drug products including therapeutic proteins and peptides based on literature and FDA database. The PK data after abdominal injection was used as a reference to determine the relative bioavailability of SC injections to the arm and thigh. The survey retrieved 19 immunoglobulin G (IgGs), 18 peptides/small proteins (molecular weight < 16 kDa), and 8 non-IgG proteins that had available clinical PK data from multiple SC injection sites. Among these, 5 (26%) IgGs, 9 (50%) peptides/small proteins, and 3 (38%) non-IgG proteins, exhibited injection site-dependent PK (i.e. PK differed by injection sites). Correlation analyses revealed that the PK of peptides/small proteins undergoing rapid SC absorption (Tmax ≤ 2 h), elimination (CL/F ≥ 39 L/h) or low plasma protein binding were more sensitive to injection sites. Similarly, non-IgG proteins (molecular weight ≥ 16 kDa) with high CL/F and low Tmax are associated with high risk of injection site-dependent SC absorption. IgGs with T1/2 < 15 days or Tmax < 5 days are more likely to show injection site-dependent SC absorption. Positive charge of the drug molecule (isoelectric point ≥8) may reduce SC absorption from all three injection sites but is not associated with high risk of injection site-dependent SC absorption. In summary, the results suggested that regional differences in pre-systemic catabolism and local SC blood flow potentially contribute injection site-dependent SC absorption of peptides/small proteins while local lymphatic flow and FcRn binding likely contribute to site-dependent SC absorption of IgGs. Wang, Fuyuan oth Wang, Jie oth Lu, Yanhui oth Tran, Doanh oth Seo, Shirley K. oth Enthalten in Elsevier Moschini, M. ELSEVIER 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up 2015 official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems New York, NY [u.a.] (DE-627)ELV012920894 volume:336 year:2021 day:10 month:08 pages:310-321 extent:12 https://doi.org/10.1016/j.jconrel.2021.06.038 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_22 GBV_ILN_40 GBV_ILN_105 35.80 Makromolekulare Chemie VZ AR 336 2021 10 0810 310-321 12 |
| spelling |
10.1016/j.jconrel.2021.06.038 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001481.pica (DE-627)ELV054897564 (ELSEVIER)S0168-3659(21)00336-9 DE-627 ger DE-627 rakwb eng 610 VZ 670 VZ 35.80 bkl Zou, Peng verfasserin aut Impact of injection sites on clinical pharmacokinetics of subcutaneously administered peptides and proteins 2021transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier For most approved subcutaneously (SC) administered drug products in the US, the recommended injection sites (i.e., abdomen, thigh, and upper arm) are usually based on experience from phase 3 trials. Relative bioavailability data directly comparing the pharmacokinetics (PK) of different SC injection sites are often not available and the underlying mechanisms that may affect SC absorption have not been systematically investigated. In this study, we surveyed clinical PK data (AUC, Cmax, and Tmax) for SC administered drug products including therapeutic proteins and peptides based on literature and FDA database. The PK data after abdominal injection was used as a reference to determine the relative bioavailability of SC injections to the arm and thigh. The survey retrieved 19 immunoglobulin G (IgGs), 18 peptides/small proteins (molecular weight < 16 kDa), and 8 non-IgG proteins that had available clinical PK data from multiple SC injection sites. Among these, 5 (26%) IgGs, 9 (50%) peptides/small proteins, and 3 (38%) non-IgG proteins, exhibited injection site-dependent PK (i.e. PK differed by injection sites). Correlation analyses revealed that the PK of peptides/small proteins undergoing rapid SC absorption (Tmax ≤ 2 h), elimination (CL/F ≥ 39 L/h) or low plasma protein binding were more sensitive to injection sites. Similarly, non-IgG proteins (molecular weight ≥ 16 kDa) with high CL/F and low Tmax are associated with high risk of injection site-dependent SC absorption. IgGs with T1/2 < 15 days or Tmax < 5 days are more likely to show injection site-dependent SC absorption. Positive charge of the drug molecule (isoelectric point ≥8) may reduce SC absorption from all three injection sites but is not associated with high risk of injection site-dependent SC absorption. In summary, the results suggested that regional differences in pre-systemic catabolism and local SC blood flow potentially contribute injection site-dependent SC absorption of peptides/small proteins while local lymphatic flow and FcRn binding likely contribute to site-dependent SC absorption of IgGs. For most approved subcutaneously (SC) administered drug products in the US, the recommended injection sites (i.e., abdomen, thigh, and upper arm) are usually based on experience from phase 3 trials. Relative bioavailability data directly comparing the pharmacokinetics (PK) of different SC injection sites are often not available and the underlying mechanisms that may affect SC absorption have not been systematically investigated. In this study, we surveyed clinical PK data (AUC, Cmax, and Tmax) for SC administered drug products including therapeutic proteins and peptides based on literature and FDA database. The PK data after abdominal injection was used as a reference to determine the relative bioavailability of SC injections to the arm and thigh. The survey retrieved 19 immunoglobulin G (IgGs), 18 peptides/small proteins (molecular weight < 16 kDa), and 8 non-IgG proteins that had available clinical PK data from multiple SC injection sites. Among these, 5 (26%) IgGs, 9 (50%) peptides/small proteins, and 3 (38%) non-IgG proteins, exhibited injection site-dependent PK (i.e. PK differed by injection sites). Correlation analyses revealed that the PK of peptides/small proteins undergoing rapid SC absorption (Tmax ≤ 2 h), elimination (CL/F ≥ 39 L/h) or low plasma protein binding were more sensitive to injection sites. Similarly, non-IgG proteins (molecular weight ≥ 16 kDa) with high CL/F and low Tmax are associated with high risk of injection site-dependent SC absorption. IgGs with T1/2 < 15 days or Tmax < 5 days are more likely to show injection site-dependent SC absorption. Positive charge of the drug molecule (isoelectric point ≥8) may reduce SC absorption from all three injection sites but is not associated with high risk of injection site-dependent SC absorption. In summary, the results suggested that regional differences in pre-systemic catabolism and local SC blood flow potentially contribute injection site-dependent SC absorption of peptides/small proteins while local lymphatic flow and FcRn binding likely contribute to site-dependent SC absorption of IgGs. Wang, Fuyuan oth Wang, Jie oth Lu, Yanhui oth Tran, Doanh oth Seo, Shirley K. oth Enthalten in Elsevier Moschini, M. ELSEVIER 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up 2015 official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems New York, NY [u.a.] (DE-627)ELV012920894 volume:336 year:2021 day:10 month:08 pages:310-321 extent:12 https://doi.org/10.1016/j.jconrel.2021.06.038 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_22 GBV_ILN_40 GBV_ILN_105 35.80 Makromolekulare Chemie VZ AR 336 2021 10 0810 310-321 12 |
| allfields_unstemmed |
10.1016/j.jconrel.2021.06.038 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001481.pica (DE-627)ELV054897564 (ELSEVIER)S0168-3659(21)00336-9 DE-627 ger DE-627 rakwb eng 610 VZ 670 VZ 35.80 bkl Zou, Peng verfasserin aut Impact of injection sites on clinical pharmacokinetics of subcutaneously administered peptides and proteins 2021transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier For most approved subcutaneously (SC) administered drug products in the US, the recommended injection sites (i.e., abdomen, thigh, and upper arm) are usually based on experience from phase 3 trials. Relative bioavailability data directly comparing the pharmacokinetics (PK) of different SC injection sites are often not available and the underlying mechanisms that may affect SC absorption have not been systematically investigated. In this study, we surveyed clinical PK data (AUC, Cmax, and Tmax) for SC administered drug products including therapeutic proteins and peptides based on literature and FDA database. The PK data after abdominal injection was used as a reference to determine the relative bioavailability of SC injections to the arm and thigh. The survey retrieved 19 immunoglobulin G (IgGs), 18 peptides/small proteins (molecular weight < 16 kDa), and 8 non-IgG proteins that had available clinical PK data from multiple SC injection sites. Among these, 5 (26%) IgGs, 9 (50%) peptides/small proteins, and 3 (38%) non-IgG proteins, exhibited injection site-dependent PK (i.e. PK differed by injection sites). Correlation analyses revealed that the PK of peptides/small proteins undergoing rapid SC absorption (Tmax ≤ 2 h), elimination (CL/F ≥ 39 L/h) or low plasma protein binding were more sensitive to injection sites. Similarly, non-IgG proteins (molecular weight ≥ 16 kDa) with high CL/F and low Tmax are associated with high risk of injection site-dependent SC absorption. IgGs with T1/2 < 15 days or Tmax < 5 days are more likely to show injection site-dependent SC absorption. Positive charge of the drug molecule (isoelectric point ≥8) may reduce SC absorption from all three injection sites but is not associated with high risk of injection site-dependent SC absorption. In summary, the results suggested that regional differences in pre-systemic catabolism and local SC blood flow potentially contribute injection site-dependent SC absorption of peptides/small proteins while local lymphatic flow and FcRn binding likely contribute to site-dependent SC absorption of IgGs. For most approved subcutaneously (SC) administered drug products in the US, the recommended injection sites (i.e., abdomen, thigh, and upper arm) are usually based on experience from phase 3 trials. Relative bioavailability data directly comparing the pharmacokinetics (PK) of different SC injection sites are often not available and the underlying mechanisms that may affect SC absorption have not been systematically investigated. In this study, we surveyed clinical PK data (AUC, Cmax, and Tmax) for SC administered drug products including therapeutic proteins and peptides based on literature and FDA database. The PK data after abdominal injection was used as a reference to determine the relative bioavailability of SC injections to the arm and thigh. The survey retrieved 19 immunoglobulin G (IgGs), 18 peptides/small proteins (molecular weight < 16 kDa), and 8 non-IgG proteins that had available clinical PK data from multiple SC injection sites. Among these, 5 (26%) IgGs, 9 (50%) peptides/small proteins, and 3 (38%) non-IgG proteins, exhibited injection site-dependent PK (i.e. PK differed by injection sites). Correlation analyses revealed that the PK of peptides/small proteins undergoing rapid SC absorption (Tmax ≤ 2 h), elimination (CL/F ≥ 39 L/h) or low plasma protein binding were more sensitive to injection sites. Similarly, non-IgG proteins (molecular weight ≥ 16 kDa) with high CL/F and low Tmax are associated with high risk of injection site-dependent SC absorption. IgGs with T1/2 < 15 days or Tmax < 5 days are more likely to show injection site-dependent SC absorption. Positive charge of the drug molecule (isoelectric point ≥8) may reduce SC absorption from all three injection sites but is not associated with high risk of injection site-dependent SC absorption. In summary, the results suggested that regional differences in pre-systemic catabolism and local SC blood flow potentially contribute injection site-dependent SC absorption of peptides/small proteins while local lymphatic flow and FcRn binding likely contribute to site-dependent SC absorption of IgGs. Wang, Fuyuan oth Wang, Jie oth Lu, Yanhui oth Tran, Doanh oth Seo, Shirley K. oth Enthalten in Elsevier Moschini, M. ELSEVIER 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up 2015 official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems New York, NY [u.a.] (DE-627)ELV012920894 volume:336 year:2021 day:10 month:08 pages:310-321 extent:12 https://doi.org/10.1016/j.jconrel.2021.06.038 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_22 GBV_ILN_40 GBV_ILN_105 35.80 Makromolekulare Chemie VZ AR 336 2021 10 0810 310-321 12 |
| allfieldsGer |
10.1016/j.jconrel.2021.06.038 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001481.pica (DE-627)ELV054897564 (ELSEVIER)S0168-3659(21)00336-9 DE-627 ger DE-627 rakwb eng 610 VZ 670 VZ 35.80 bkl Zou, Peng verfasserin aut Impact of injection sites on clinical pharmacokinetics of subcutaneously administered peptides and proteins 2021transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier For most approved subcutaneously (SC) administered drug products in the US, the recommended injection sites (i.e., abdomen, thigh, and upper arm) are usually based on experience from phase 3 trials. Relative bioavailability data directly comparing the pharmacokinetics (PK) of different SC injection sites are often not available and the underlying mechanisms that may affect SC absorption have not been systematically investigated. In this study, we surveyed clinical PK data (AUC, Cmax, and Tmax) for SC administered drug products including therapeutic proteins and peptides based on literature and FDA database. The PK data after abdominal injection was used as a reference to determine the relative bioavailability of SC injections to the arm and thigh. The survey retrieved 19 immunoglobulin G (IgGs), 18 peptides/small proteins (molecular weight < 16 kDa), and 8 non-IgG proteins that had available clinical PK data from multiple SC injection sites. Among these, 5 (26%) IgGs, 9 (50%) peptides/small proteins, and 3 (38%) non-IgG proteins, exhibited injection site-dependent PK (i.e. PK differed by injection sites). Correlation analyses revealed that the PK of peptides/small proteins undergoing rapid SC absorption (Tmax ≤ 2 h), elimination (CL/F ≥ 39 L/h) or low plasma protein binding were more sensitive to injection sites. Similarly, non-IgG proteins (molecular weight ≥ 16 kDa) with high CL/F and low Tmax are associated with high risk of injection site-dependent SC absorption. IgGs with T1/2 < 15 days or Tmax < 5 days are more likely to show injection site-dependent SC absorption. Positive charge of the drug molecule (isoelectric point ≥8) may reduce SC absorption from all three injection sites but is not associated with high risk of injection site-dependent SC absorption. In summary, the results suggested that regional differences in pre-systemic catabolism and local SC blood flow potentially contribute injection site-dependent SC absorption of peptides/small proteins while local lymphatic flow and FcRn binding likely contribute to site-dependent SC absorption of IgGs. For most approved subcutaneously (SC) administered drug products in the US, the recommended injection sites (i.e., abdomen, thigh, and upper arm) are usually based on experience from phase 3 trials. Relative bioavailability data directly comparing the pharmacokinetics (PK) of different SC injection sites are often not available and the underlying mechanisms that may affect SC absorption have not been systematically investigated. In this study, we surveyed clinical PK data (AUC, Cmax, and Tmax) for SC administered drug products including therapeutic proteins and peptides based on literature and FDA database. The PK data after abdominal injection was used as a reference to determine the relative bioavailability of SC injections to the arm and thigh. The survey retrieved 19 immunoglobulin G (IgGs), 18 peptides/small proteins (molecular weight < 16 kDa), and 8 non-IgG proteins that had available clinical PK data from multiple SC injection sites. Among these, 5 (26%) IgGs, 9 (50%) peptides/small proteins, and 3 (38%) non-IgG proteins, exhibited injection site-dependent PK (i.e. PK differed by injection sites). Correlation analyses revealed that the PK of peptides/small proteins undergoing rapid SC absorption (Tmax ≤ 2 h), elimination (CL/F ≥ 39 L/h) or low plasma protein binding were more sensitive to injection sites. Similarly, non-IgG proteins (molecular weight ≥ 16 kDa) with high CL/F and low Tmax are associated with high risk of injection site-dependent SC absorption. IgGs with T1/2 < 15 days or Tmax < 5 days are more likely to show injection site-dependent SC absorption. Positive charge of the drug molecule (isoelectric point ≥8) may reduce SC absorption from all three injection sites but is not associated with high risk of injection site-dependent SC absorption. In summary, the results suggested that regional differences in pre-systemic catabolism and local SC blood flow potentially contribute injection site-dependent SC absorption of peptides/small proteins while local lymphatic flow and FcRn binding likely contribute to site-dependent SC absorption of IgGs. Wang, Fuyuan oth Wang, Jie oth Lu, Yanhui oth Tran, Doanh oth Seo, Shirley K. oth Enthalten in Elsevier Moschini, M. ELSEVIER 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up 2015 official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems New York, NY [u.a.] (DE-627)ELV012920894 volume:336 year:2021 day:10 month:08 pages:310-321 extent:12 https://doi.org/10.1016/j.jconrel.2021.06.038 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_22 GBV_ILN_40 GBV_ILN_105 35.80 Makromolekulare Chemie VZ AR 336 2021 10 0810 310-321 12 |
| allfieldsSound |
10.1016/j.jconrel.2021.06.038 doi /cbs_pica/cbs_olc/import_discovery/elsevier/einzuspielen/GBV00000000001481.pica (DE-627)ELV054897564 (ELSEVIER)S0168-3659(21)00336-9 DE-627 ger DE-627 rakwb eng 610 VZ 670 VZ 35.80 bkl Zou, Peng verfasserin aut Impact of injection sites on clinical pharmacokinetics of subcutaneously administered peptides and proteins 2021transfer abstract 12 nicht spezifiziert zzz rdacontent nicht spezifiziert z rdamedia nicht spezifiziert zu rdacarrier For most approved subcutaneously (SC) administered drug products in the US, the recommended injection sites (i.e., abdomen, thigh, and upper arm) are usually based on experience from phase 3 trials. Relative bioavailability data directly comparing the pharmacokinetics (PK) of different SC injection sites are often not available and the underlying mechanisms that may affect SC absorption have not been systematically investigated. In this study, we surveyed clinical PK data (AUC, Cmax, and Tmax) for SC administered drug products including therapeutic proteins and peptides based on literature and FDA database. The PK data after abdominal injection was used as a reference to determine the relative bioavailability of SC injections to the arm and thigh. The survey retrieved 19 immunoglobulin G (IgGs), 18 peptides/small proteins (molecular weight < 16 kDa), and 8 non-IgG proteins that had available clinical PK data from multiple SC injection sites. Among these, 5 (26%) IgGs, 9 (50%) peptides/small proteins, and 3 (38%) non-IgG proteins, exhibited injection site-dependent PK (i.e. PK differed by injection sites). Correlation analyses revealed that the PK of peptides/small proteins undergoing rapid SC absorption (Tmax ≤ 2 h), elimination (CL/F ≥ 39 L/h) or low plasma protein binding were more sensitive to injection sites. Similarly, non-IgG proteins (molecular weight ≥ 16 kDa) with high CL/F and low Tmax are associated with high risk of injection site-dependent SC absorption. IgGs with T1/2 < 15 days or Tmax < 5 days are more likely to show injection site-dependent SC absorption. Positive charge of the drug molecule (isoelectric point ≥8) may reduce SC absorption from all three injection sites but is not associated with high risk of injection site-dependent SC absorption. In summary, the results suggested that regional differences in pre-systemic catabolism and local SC blood flow potentially contribute injection site-dependent SC absorption of peptides/small proteins while local lymphatic flow and FcRn binding likely contribute to site-dependent SC absorption of IgGs. For most approved subcutaneously (SC) administered drug products in the US, the recommended injection sites (i.e., abdomen, thigh, and upper arm) are usually based on experience from phase 3 trials. Relative bioavailability data directly comparing the pharmacokinetics (PK) of different SC injection sites are often not available and the underlying mechanisms that may affect SC absorption have not been systematically investigated. In this study, we surveyed clinical PK data (AUC, Cmax, and Tmax) for SC administered drug products including therapeutic proteins and peptides based on literature and FDA database. The PK data after abdominal injection was used as a reference to determine the relative bioavailability of SC injections to the arm and thigh. The survey retrieved 19 immunoglobulin G (IgGs), 18 peptides/small proteins (molecular weight < 16 kDa), and 8 non-IgG proteins that had available clinical PK data from multiple SC injection sites. Among these, 5 (26%) IgGs, 9 (50%) peptides/small proteins, and 3 (38%) non-IgG proteins, exhibited injection site-dependent PK (i.e. PK differed by injection sites). Correlation analyses revealed that the PK of peptides/small proteins undergoing rapid SC absorption (Tmax ≤ 2 h), elimination (CL/F ≥ 39 L/h) or low plasma protein binding were more sensitive to injection sites. Similarly, non-IgG proteins (molecular weight ≥ 16 kDa) with high CL/F and low Tmax are associated with high risk of injection site-dependent SC absorption. IgGs with T1/2 < 15 days or Tmax < 5 days are more likely to show injection site-dependent SC absorption. Positive charge of the drug molecule (isoelectric point ≥8) may reduce SC absorption from all three injection sites but is not associated with high risk of injection site-dependent SC absorption. In summary, the results suggested that regional differences in pre-systemic catabolism and local SC blood flow potentially contribute injection site-dependent SC absorption of peptides/small proteins while local lymphatic flow and FcRn binding likely contribute to site-dependent SC absorption of IgGs. Wang, Fuyuan oth Wang, Jie oth Lu, Yanhui oth Tran, Doanh oth Seo, Shirley K. oth Enthalten in Elsevier Moschini, M. ELSEVIER 537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up 2015 official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems New York, NY [u.a.] (DE-627)ELV012920894 volume:336 year:2021 day:10 month:08 pages:310-321 extent:12 https://doi.org/10.1016/j.jconrel.2021.06.038 Volltext GBV_USEFLAG_U GBV_ELV SYSFLAG_U GBV_ILN_22 GBV_ILN_40 GBV_ILN_105 35.80 Makromolekulare Chemie VZ AR 336 2021 10 0810 310-321 12 |
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impact of injection sites on clinical pharmacokinetics of subcutaneously administered peptides and proteins |
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Impact of injection sites on clinical pharmacokinetics of subcutaneously administered peptides and proteins |
| abstract |
For most approved subcutaneously (SC) administered drug products in the US, the recommended injection sites (i.e., abdomen, thigh, and upper arm) are usually based on experience from phase 3 trials. Relative bioavailability data directly comparing the pharmacokinetics (PK) of different SC injection sites are often not available and the underlying mechanisms that may affect SC absorption have not been systematically investigated. In this study, we surveyed clinical PK data (AUC, Cmax, and Tmax) for SC administered drug products including therapeutic proteins and peptides based on literature and FDA database. The PK data after abdominal injection was used as a reference to determine the relative bioavailability of SC injections to the arm and thigh. The survey retrieved 19 immunoglobulin G (IgGs), 18 peptides/small proteins (molecular weight < 16 kDa), and 8 non-IgG proteins that had available clinical PK data from multiple SC injection sites. Among these, 5 (26%) IgGs, 9 (50%) peptides/small proteins, and 3 (38%) non-IgG proteins, exhibited injection site-dependent PK (i.e. PK differed by injection sites). Correlation analyses revealed that the PK of peptides/small proteins undergoing rapid SC absorption (Tmax ≤ 2 h), elimination (CL/F ≥ 39 L/h) or low plasma protein binding were more sensitive to injection sites. Similarly, non-IgG proteins (molecular weight ≥ 16 kDa) with high CL/F and low Tmax are associated with high risk of injection site-dependent SC absorption. IgGs with T1/2 < 15 days or Tmax < 5 days are more likely to show injection site-dependent SC absorption. Positive charge of the drug molecule (isoelectric point ≥8) may reduce SC absorption from all three injection sites but is not associated with high risk of injection site-dependent SC absorption. In summary, the results suggested that regional differences in pre-systemic catabolism and local SC blood flow potentially contribute injection site-dependent SC absorption of peptides/small proteins while local lymphatic flow and FcRn binding likely contribute to site-dependent SC absorption of IgGs. |
| abstractGer |
For most approved subcutaneously (SC) administered drug products in the US, the recommended injection sites (i.e., abdomen, thigh, and upper arm) are usually based on experience from phase 3 trials. Relative bioavailability data directly comparing the pharmacokinetics (PK) of different SC injection sites are often not available and the underlying mechanisms that may affect SC absorption have not been systematically investigated. In this study, we surveyed clinical PK data (AUC, Cmax, and Tmax) for SC administered drug products including therapeutic proteins and peptides based on literature and FDA database. The PK data after abdominal injection was used as a reference to determine the relative bioavailability of SC injections to the arm and thigh. The survey retrieved 19 immunoglobulin G (IgGs), 18 peptides/small proteins (molecular weight < 16 kDa), and 8 non-IgG proteins that had available clinical PK data from multiple SC injection sites. Among these, 5 (26%) IgGs, 9 (50%) peptides/small proteins, and 3 (38%) non-IgG proteins, exhibited injection site-dependent PK (i.e. PK differed by injection sites). Correlation analyses revealed that the PK of peptides/small proteins undergoing rapid SC absorption (Tmax ≤ 2 h), elimination (CL/F ≥ 39 L/h) or low plasma protein binding were more sensitive to injection sites. Similarly, non-IgG proteins (molecular weight ≥ 16 kDa) with high CL/F and low Tmax are associated with high risk of injection site-dependent SC absorption. IgGs with T1/2 < 15 days or Tmax < 5 days are more likely to show injection site-dependent SC absorption. Positive charge of the drug molecule (isoelectric point ≥8) may reduce SC absorption from all three injection sites but is not associated with high risk of injection site-dependent SC absorption. In summary, the results suggested that regional differences in pre-systemic catabolism and local SC blood flow potentially contribute injection site-dependent SC absorption of peptides/small proteins while local lymphatic flow and FcRn binding likely contribute to site-dependent SC absorption of IgGs. |
| abstract_unstemmed |
For most approved subcutaneously (SC) administered drug products in the US, the recommended injection sites (i.e., abdomen, thigh, and upper arm) are usually based on experience from phase 3 trials. Relative bioavailability data directly comparing the pharmacokinetics (PK) of different SC injection sites are often not available and the underlying mechanisms that may affect SC absorption have not been systematically investigated. In this study, we surveyed clinical PK data (AUC, Cmax, and Tmax) for SC administered drug products including therapeutic proteins and peptides based on literature and FDA database. The PK data after abdominal injection was used as a reference to determine the relative bioavailability of SC injections to the arm and thigh. The survey retrieved 19 immunoglobulin G (IgGs), 18 peptides/small proteins (molecular weight < 16 kDa), and 8 non-IgG proteins that had available clinical PK data from multiple SC injection sites. Among these, 5 (26%) IgGs, 9 (50%) peptides/small proteins, and 3 (38%) non-IgG proteins, exhibited injection site-dependent PK (i.e. PK differed by injection sites). Correlation analyses revealed that the PK of peptides/small proteins undergoing rapid SC absorption (Tmax ≤ 2 h), elimination (CL/F ≥ 39 L/h) or low plasma protein binding were more sensitive to injection sites. Similarly, non-IgG proteins (molecular weight ≥ 16 kDa) with high CL/F and low Tmax are associated with high risk of injection site-dependent SC absorption. IgGs with T1/2 < 15 days or Tmax < 5 days are more likely to show injection site-dependent SC absorption. Positive charge of the drug molecule (isoelectric point ≥8) may reduce SC absorption from all three injection sites but is not associated with high risk of injection site-dependent SC absorption. In summary, the results suggested that regional differences in pre-systemic catabolism and local SC blood flow potentially contribute injection site-dependent SC absorption of peptides/small proteins while local lymphatic flow and FcRn binding likely contribute to site-dependent SC absorption of IgGs. |
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Correlation analyses revealed that the PK of peptides/small proteins undergoing rapid SC absorption (Tmax ≤ 2 h), elimination (CL/F ≥ 39 L/h) or low plasma protein binding were more sensitive to injection sites. Similarly, non-IgG proteins (molecular weight ≥ 16 kDa) with high CL/F and low Tmax are associated with high risk of injection site-dependent SC absorption. IgGs with T1/2 < 15 days or Tmax < 5 days are more likely to show injection site-dependent SC absorption. Positive charge of the drug molecule (isoelectric point ≥8) may reduce SC absorption from all three injection sites but is not associated with high risk of injection site-dependent SC absorption. In summary, the results suggested that regional differences in pre-systemic catabolism and local SC blood flow potentially contribute injection site-dependent SC absorption of peptides/small proteins while local lymphatic flow and FcRn binding likely contribute to site-dependent SC absorption of IgGs.</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">For most approved subcutaneously (SC) administered drug products in the US, the recommended injection sites (i.e., abdomen, thigh, and upper arm) are usually based on experience from phase 3 trials. Relative bioavailability data directly comparing the pharmacokinetics (PK) of different SC injection sites are often not available and the underlying mechanisms that may affect SC absorption have not been systematically investigated. In this study, we surveyed clinical PK data (AUC, Cmax, and Tmax) for SC administered drug products including therapeutic proteins and peptides based on literature and FDA database. The PK data after abdominal injection was used as a reference to determine the relative bioavailability of SC injections to the arm and thigh. The survey retrieved 19 immunoglobulin G (IgGs), 18 peptides/small proteins (molecular weight < 16 kDa), and 8 non-IgG proteins that had available clinical PK data from multiple SC injection sites. Among these, 5 (26%) IgGs, 9 (50%) peptides/small proteins, and 3 (38%) non-IgG proteins, exhibited injection site-dependent PK (i.e. PK differed by injection sites). Correlation analyses revealed that the PK of peptides/small proteins undergoing rapid SC absorption (Tmax ≤ 2 h), elimination (CL/F ≥ 39 L/h) or low plasma protein binding were more sensitive to injection sites. Similarly, non-IgG proteins (molecular weight ≥ 16 kDa) with high CL/F and low Tmax are associated with high risk of injection site-dependent SC absorption. IgGs with T1/2 < 15 days or Tmax < 5 days are more likely to show injection site-dependent SC absorption. Positive charge of the drug molecule (isoelectric point ≥8) may reduce SC absorption from all three injection sites but is not associated with high risk of injection site-dependent SC absorption. In summary, the results suggested that regional differences in pre-systemic catabolism and local SC blood flow potentially contribute injection site-dependent SC absorption of peptides/small proteins while local lymphatic flow and FcRn binding likely contribute to site-dependent SC absorption of IgGs.</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wang, Fuyuan</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Wang, Jie</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Lu, Yanhui</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Tran, Doanh</subfield><subfield code="4">oth</subfield></datafield><datafield tag="700" ind1="1" ind2=" "><subfield code="a">Seo, Shirley K.</subfield><subfield code="4">oth</subfield></datafield><datafield tag="773" ind1="0" ind2="8"><subfield code="i">Enthalten in</subfield><subfield code="n">Elsevier</subfield><subfield code="a">Moschini, M. ELSEVIER</subfield><subfield code="t">537 Early, intermediate and late recurrence after radical cystectomy due to bladder cancer: The necessity of a tailored follow up</subfield><subfield code="d">2015</subfield><subfield code="d">official journal of the Controlled Release Society and of the Japanese Society of Drug Delivery Systems</subfield><subfield code="g">New York, NY [u.a.]</subfield><subfield code="w">(DE-627)ELV012920894</subfield></datafield><datafield tag="773" ind1="1" ind2="8"><subfield code="g">volume:336</subfield><subfield code="g">year:2021</subfield><subfield code="g">day:10</subfield><subfield code="g">month:08</subfield><subfield code="g">pages:310-321</subfield><subfield code="g">extent:12</subfield></datafield><datafield tag="856" ind1="4" ind2="0"><subfield code="u">https://doi.org/10.1016/j.jconrel.2021.06.038</subfield><subfield code="3">Volltext</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_USEFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ELV</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">SYSFLAG_U</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_22</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_40</subfield></datafield><datafield tag="912" ind1=" " ind2=" "><subfield code="a">GBV_ILN_105</subfield></datafield><datafield tag="936" ind1="b" ind2="k"><subfield code="a">35.80</subfield><subfield code="j">Makromolekulare Chemie</subfield><subfield code="q">VZ</subfield></datafield><datafield tag="951" ind1=" " ind2=" "><subfield code="a">AR</subfield></datafield><datafield tag="952" ind1=" " ind2=" "><subfield code="d">336</subfield><subfield code="j">2021</subfield><subfield code="b">10</subfield><subfield code="c">0810</subfield><subfield code="h">310-321</subfield><subfield code="g">12</subfield></datafield></record></collection>
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