Rheumatoid arthritis downregulates the drug transporter OATP1B1: Fluvastatin as a probe

Aims: Rheumatoid arthritis (RA) is a long term autoimmune inflammatory disease characterized by high autoantibody production and cytokine release, especially IL-6 and TNF-α. Some clinical studies have shown the effect of RA on CYP metabolism. However, the effect of RA on the drug transporter OATP1B1...
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Autor*in:	Caris, Juciene Aparecida [verfasserIn] Benzi, Jhohann Richard de Lima [verfasserIn] de Souza, Flávio Falcão Lima [verfasserIn] de Oliveira, Renê Donizeti Ribeiro [verfasserIn] Donadi, Eduardo Antônio [verfasserIn] Lanchote, Vera Lucia [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2020

Schlagwörter:	Rheumatoid arthritis OATP1B1 Fluvastatin Enantiomers Inflammation

Übergeordnetes Werk:	Enthalten in: European journal of pharmaceutical sciences - New York, NY [u.a.] : Elsevier, 1993, 146
Übergeordnetes Werk:	volume:146

DOI / URN:	10.1016/j.ejps.2020.105264

Katalog-ID:	ELV003827151

Internformat


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024	7		\|a 10.1016/j.ejps.2020.105264 \|2 doi
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035			\|a (ELSEVIER)S0928-0987(20)30053-1
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245	1	0	\|a Rheumatoid arthritis downregulates the drug transporter OATP1B1: Fluvastatin as a probe
264		1	\|c 2020
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337			\|a Computermedien \|b c \|2 rdamedia
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520			\|a Aims: Rheumatoid arthritis (RA) is a long term autoimmune inflammatory disease characterized by high autoantibody production and cytokine release, especially IL-6 and TNF-α. Some clinical studies have shown the effect of RA on CYP metabolism. However, the effect of RA on the drug transporter OATP1B1 remains a gap.Methods: Patients with RA under pharmacological treatment (n = 10) and healthy volunteers (n = 15) treated for seven consecutive days with racemic fluvastatin (20, 40, or 80 mg/24 h) were investigated. Serial blood samples were collected during the last dose interval. All participants were assessed for cytokine profile and CYP2C9 genotype.Results: Patients with RA showed increased plasma concentrations of IFN-γ and TNF-α up to two and four times, respectively, when compared to healthy volunteers, whereas CYP2C9 activity based on genotype was considered normal or slightly reduced for both investigated groups. When compared to healthy volunteers, patients with RA presented higher values (median and 25th–75th percentiles) of normalized AUC for 20 mg dose (250 [114–405] vs. 96.7 [78.1–131] ng h mL−1 for (−)-3S,5R-fluvastatin and 163 [96.9–325] vs. 83.1 [61.7–107] ng⋅h⋅mL−1 for (+)-3R,5S-fluvastatin) and lower values of CL/F (40.9 [24.5–89.1] vs. 103 [75.9–128] L⋅h−1 for (−)-3S,5R-fluvastatin and 61.4 [30.6–103] vs. 120 [93.0–162] L⋅h−1 for (+)-3R,5S-fluvastatin) and V/F (73.0 [28.5–117] vs. 143 [108–221] L for (−)-3S,5R-fluvastatin and 93.9 [32.7–116] vs. 153 [122–234] L for (+)-3R,5S-fluvastatin) for both enantiomers.Conclusion: The lower values of CL/F and V/F for both fluvastatin enantiomers in RA patients suggest that the inflammatory disease downregulates the sinusoidal drug transporter OATP1B1, the rate-determining step in the hepatic clearance of fluvastatin.
650		4	\|a Rheumatoid arthritis
650		4	\|a OATP1B1
650		4	\|a Fluvastatin
650		4	\|a Enantiomers
650		4	\|a Inflammation
700	1		\|a Benzi, Jhohann Richard de Lima \|e verfasserin \|0 (orcid)0000-0001-6986-6193 \|4 aut
700	1		\|a de Souza, Flávio Falcão Lima \|e verfasserin \|4 aut
700	1		\|a de Oliveira, Renê Donizeti Ribeiro \|e verfasserin \|4 aut
700	1		\|a Donadi, Eduardo Antônio \|e verfasserin \|4 aut
700	1		\|a Lanchote, Vera Lucia \|e verfasserin \|0 (orcid)0000-0002-0074-4953 \|4 aut
773	0	8	\|i Enthalten in \|t European journal of pharmaceutical sciences \|d New York, NY [u.a.] : Elsevier, 1993 \|g 146 \|h Online-Ressource \|w (DE-627)300897308 \|w (DE-600)1483522-8 \|w (DE-576)094142033 \|x 1879-0720 \|7 nnns
773	1	8	\|g volume:146
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912			\|a GBV_ILN_20
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912			\|a GBV_ILN_24
912			\|a GBV_ILN_31
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912			\|a GBV_ILN_40
912			\|a GBV_ILN_60
912			\|a GBV_ILN_62
912			\|a GBV_ILN_63
912			\|a GBV_ILN_69
912			\|a GBV_ILN_70
912			\|a GBV_ILN_73
912			\|a GBV_ILN_74
912			\|a GBV_ILN_90
912			\|a GBV_ILN_95
912			\|a GBV_ILN_100
912			\|a GBV_ILN_101
912			\|a GBV_ILN_105
912			\|a GBV_ILN_110
912			\|a GBV_ILN_151
912			\|a GBV_ILN_187
912			\|a GBV_ILN_213
912			\|a GBV_ILN_224
912			\|a GBV_ILN_230
912			\|a GBV_ILN_370
912			\|a GBV_ILN_602
912			\|a GBV_ILN_702
912			\|a GBV_ILN_2001
912			\|a GBV_ILN_2003
912			\|a GBV_ILN_2004
912			\|a GBV_ILN_2005
912			\|a GBV_ILN_2007
912			\|a GBV_ILN_2008
912			\|a GBV_ILN_2009
912			\|a GBV_ILN_2010
912			\|a GBV_ILN_2011
912			\|a GBV_ILN_2014
912			\|a GBV_ILN_2015
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912			\|a GBV_ILN_2021
912			\|a GBV_ILN_2025
912			\|a GBV_ILN_2026
912			\|a GBV_ILN_2027
912			\|a GBV_ILN_2034
912			\|a GBV_ILN_2038
912			\|a GBV_ILN_2044
912			\|a GBV_ILN_2048
912			\|a GBV_ILN_2049
912			\|a GBV_ILN_2050
912			\|a GBV_ILN_2055
912			\|a GBV_ILN_2056
912			\|a GBV_ILN_2059
912			\|a GBV_ILN_2061
912			\|a GBV_ILN_2064
912			\|a GBV_ILN_2065
912			\|a GBV_ILN_2068
912			\|a GBV_ILN_2088
912			\|a GBV_ILN_2106
912			\|a GBV_ILN_2110
912			\|a GBV_ILN_2111
912			\|a GBV_ILN_2112
912			\|a GBV_ILN_2113
912			\|a GBV_ILN_2118
912			\|a GBV_ILN_2122
912			\|a GBV_ILN_2129
912			\|a GBV_ILN_2143
912			\|a GBV_ILN_2147
912			\|a GBV_ILN_2148
912			\|a GBV_ILN_2152
912			\|a GBV_ILN_2153
912			\|a GBV_ILN_2190
912			\|a GBV_ILN_2232
912			\|a GBV_ILN_2336
912			\|a GBV_ILN_2470
912			\|a GBV_ILN_2507
912			\|a GBV_ILN_2522
912			\|a GBV_ILN_4035
912			\|a GBV_ILN_4037
912			\|a GBV_ILN_4112
912			\|a GBV_ILN_4125
912			\|a GBV_ILN_4126
912			\|a GBV_ILN_4242
912			\|a GBV_ILN_4249
912			\|a GBV_ILN_4251
912			\|a GBV_ILN_4305
912			\|a GBV_ILN_4306
912			\|a GBV_ILN_4307
912			\|a GBV_ILN_4313
912			\|a GBV_ILN_4322
912			\|a GBV_ILN_4323
912			\|a GBV_ILN_4324
912			\|a GBV_ILN_4325
912			\|a GBV_ILN_4326
912			\|a GBV_ILN_4333
912			\|a GBV_ILN_4334
912			\|a GBV_ILN_4335
912			\|a GBV_ILN_4338
912			\|a GBV_ILN_4393
912			\|a GBV_ILN_4700
936	b	k	\|a 44.40 \|j Pharmazie \|j Pharmazeutika
951			\|a AR
952			\|d 146

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author_variant	j a c ja jac j r d l b jrdl jrdlb s f f l d sffl sffld o r d r d ordr ordrd e a d ea ead v l l vl vll
matchkey_str	article:18790720:2020----::huaodrhiidwrgltshdutasotrapb
hierarchy_sort_str	2020
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publishDate	2020
allfields	10.1016/j.ejps.2020.105264 doi (DE-627)ELV003827151 (ELSEVIER)S0928-0987(20)30053-1 DE-627 ger DE-627 rda eng 610 DE-600 15,3 ssgn PHARM DE-84 fid 44.40 bkl Caris, Juciene Aparecida verfasserin aut Rheumatoid arthritis downregulates the drug transporter OATP1B1: Fluvastatin as a probe 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Aims: Rheumatoid arthritis (RA) is a long term autoimmune inflammatory disease characterized by high autoantibody production and cytokine release, especially IL-6 and TNF-α. Some clinical studies have shown the effect of RA on CYP metabolism. However, the effect of RA on the drug transporter OATP1B1 remains a gap.Methods: Patients with RA under pharmacological treatment (n = 10) and healthy volunteers (n = 15) treated for seven consecutive days with racemic fluvastatin (20, 40, or 80 mg/24 h) were investigated. Serial blood samples were collected during the last dose interval. All participants were assessed for cytokine profile and CYP2C9 genotype.Results: Patients with RA showed increased plasma concentrations of IFN-γ and TNF-α up to two and four times, respectively, when compared to healthy volunteers, whereas CYP2C9 activity based on genotype was considered normal or slightly reduced for both investigated groups. When compared to healthy volunteers, patients with RA presented higher values (median and 25th–75th percentiles) of normalized AUC for 20 mg dose (250 [114–405] vs. 96.7 [78.1–131] ng h mL−1 for (−)-3S,5R-fluvastatin and 163 [96.9–325] vs. 83.1 [61.7–107] ng⋅h⋅mL−1 for (+)-3R,5S-fluvastatin) and lower values of CL/F (40.9 [24.5–89.1] vs. 103 [75.9–128] L⋅h−1 for (−)-3S,5R-fluvastatin and 61.4 [30.6–103] vs. 120 [93.0–162] L⋅h−1 for (+)-3R,5S-fluvastatin) and V/F (73.0 [28.5–117] vs. 143 [108–221] L for (−)-3S,5R-fluvastatin and 93.9 [32.7–116] vs. 153 [122–234] L for (+)-3R,5S-fluvastatin) for both enantiomers.Conclusion: The lower values of CL/F and V/F for both fluvastatin enantiomers in RA patients suggest that the inflammatory disease downregulates the sinusoidal drug transporter OATP1B1, the rate-determining step in the hepatic clearance of fluvastatin. Rheumatoid arthritis OATP1B1 Fluvastatin Enantiomers Inflammation Benzi, Jhohann Richard de Lima verfasserin (orcid)0000-0001-6986-6193 aut de Souza, Flávio Falcão Lima verfasserin aut de Oliveira, Renê Donizeti Ribeiro verfasserin aut Donadi, Eduardo Antônio verfasserin aut Lanchote, Vera Lucia verfasserin (orcid)0000-0002-0074-4953 aut Enthalten in European journal of pharmaceutical sciences New York, NY [u.a.] : Elsevier, 1993 146 Online-Ressource (DE-627)300897308 (DE-600)1483522-8 (DE-576)094142033 1879-0720 nnns volume:146 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika AR 146
spelling	10.1016/j.ejps.2020.105264 doi (DE-627)ELV003827151 (ELSEVIER)S0928-0987(20)30053-1 DE-627 ger DE-627 rda eng 610 DE-600 15,3 ssgn PHARM DE-84 fid 44.40 bkl Caris, Juciene Aparecida verfasserin aut Rheumatoid arthritis downregulates the drug transporter OATP1B1: Fluvastatin as a probe 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Aims: Rheumatoid arthritis (RA) is a long term autoimmune inflammatory disease characterized by high autoantibody production and cytokine release, especially IL-6 and TNF-α. Some clinical studies have shown the effect of RA on CYP metabolism. However, the effect of RA on the drug transporter OATP1B1 remains a gap.Methods: Patients with RA under pharmacological treatment (n = 10) and healthy volunteers (n = 15) treated for seven consecutive days with racemic fluvastatin (20, 40, or 80 mg/24 h) were investigated. Serial blood samples were collected during the last dose interval. All participants were assessed for cytokine profile and CYP2C9 genotype.Results: Patients with RA showed increased plasma concentrations of IFN-γ and TNF-α up to two and four times, respectively, when compared to healthy volunteers, whereas CYP2C9 activity based on genotype was considered normal or slightly reduced for both investigated groups. When compared to healthy volunteers, patients with RA presented higher values (median and 25th–75th percentiles) of normalized AUC for 20 mg dose (250 [114–405] vs. 96.7 [78.1–131] ng h mL−1 for (−)-3S,5R-fluvastatin and 163 [96.9–325] vs. 83.1 [61.7–107] ng⋅h⋅mL−1 for (+)-3R,5S-fluvastatin) and lower values of CL/F (40.9 [24.5–89.1] vs. 103 [75.9–128] L⋅h−1 for (−)-3S,5R-fluvastatin and 61.4 [30.6–103] vs. 120 [93.0–162] L⋅h−1 for (+)-3R,5S-fluvastatin) and V/F (73.0 [28.5–117] vs. 143 [108–221] L for (−)-3S,5R-fluvastatin and 93.9 [32.7–116] vs. 153 [122–234] L for (+)-3R,5S-fluvastatin) for both enantiomers.Conclusion: The lower values of CL/F and V/F for both fluvastatin enantiomers in RA patients suggest that the inflammatory disease downregulates the sinusoidal drug transporter OATP1B1, the rate-determining step in the hepatic clearance of fluvastatin. Rheumatoid arthritis OATP1B1 Fluvastatin Enantiomers Inflammation Benzi, Jhohann Richard de Lima verfasserin (orcid)0000-0001-6986-6193 aut de Souza, Flávio Falcão Lima verfasserin aut de Oliveira, Renê Donizeti Ribeiro verfasserin aut Donadi, Eduardo Antônio verfasserin aut Lanchote, Vera Lucia verfasserin (orcid)0000-0002-0074-4953 aut Enthalten in European journal of pharmaceutical sciences New York, NY [u.a.] : Elsevier, 1993 146 Online-Ressource (DE-627)300897308 (DE-600)1483522-8 (DE-576)094142033 1879-0720 nnns volume:146 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika AR 146
allfields_unstemmed	10.1016/j.ejps.2020.105264 doi (DE-627)ELV003827151 (ELSEVIER)S0928-0987(20)30053-1 DE-627 ger DE-627 rda eng 610 DE-600 15,3 ssgn PHARM DE-84 fid 44.40 bkl Caris, Juciene Aparecida verfasserin aut Rheumatoid arthritis downregulates the drug transporter OATP1B1: Fluvastatin as a probe 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Aims: Rheumatoid arthritis (RA) is a long term autoimmune inflammatory disease characterized by high autoantibody production and cytokine release, especially IL-6 and TNF-α. Some clinical studies have shown the effect of RA on CYP metabolism. However, the effect of RA on the drug transporter OATP1B1 remains a gap.Methods: Patients with RA under pharmacological treatment (n = 10) and healthy volunteers (n = 15) treated for seven consecutive days with racemic fluvastatin (20, 40, or 80 mg/24 h) were investigated. Serial blood samples were collected during the last dose interval. All participants were assessed for cytokine profile and CYP2C9 genotype.Results: Patients with RA showed increased plasma concentrations of IFN-γ and TNF-α up to two and four times, respectively, when compared to healthy volunteers, whereas CYP2C9 activity based on genotype was considered normal or slightly reduced for both investigated groups. When compared to healthy volunteers, patients with RA presented higher values (median and 25th–75th percentiles) of normalized AUC for 20 mg dose (250 [114–405] vs. 96.7 [78.1–131] ng h mL−1 for (−)-3S,5R-fluvastatin and 163 [96.9–325] vs. 83.1 [61.7–107] ng⋅h⋅mL−1 for (+)-3R,5S-fluvastatin) and lower values of CL/F (40.9 [24.5–89.1] vs. 103 [75.9–128] L⋅h−1 for (−)-3S,5R-fluvastatin and 61.4 [30.6–103] vs. 120 [93.0–162] L⋅h−1 for (+)-3R,5S-fluvastatin) and V/F (73.0 [28.5–117] vs. 143 [108–221] L for (−)-3S,5R-fluvastatin and 93.9 [32.7–116] vs. 153 [122–234] L for (+)-3R,5S-fluvastatin) for both enantiomers.Conclusion: The lower values of CL/F and V/F for both fluvastatin enantiomers in RA patients suggest that the inflammatory disease downregulates the sinusoidal drug transporter OATP1B1, the rate-determining step in the hepatic clearance of fluvastatin. Rheumatoid arthritis OATP1B1 Fluvastatin Enantiomers Inflammation Benzi, Jhohann Richard de Lima verfasserin (orcid)0000-0001-6986-6193 aut de Souza, Flávio Falcão Lima verfasserin aut de Oliveira, Renê Donizeti Ribeiro verfasserin aut Donadi, Eduardo Antônio verfasserin aut Lanchote, Vera Lucia verfasserin (orcid)0000-0002-0074-4953 aut Enthalten in European journal of pharmaceutical sciences New York, NY [u.a.] : Elsevier, 1993 146 Online-Ressource (DE-627)300897308 (DE-600)1483522-8 (DE-576)094142033 1879-0720 nnns volume:146 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika AR 146
allfieldsGer	10.1016/j.ejps.2020.105264 doi (DE-627)ELV003827151 (ELSEVIER)S0928-0987(20)30053-1 DE-627 ger DE-627 rda eng 610 DE-600 15,3 ssgn PHARM DE-84 fid 44.40 bkl Caris, Juciene Aparecida verfasserin aut Rheumatoid arthritis downregulates the drug transporter OATP1B1: Fluvastatin as a probe 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Aims: Rheumatoid arthritis (RA) is a long term autoimmune inflammatory disease characterized by high autoantibody production and cytokine release, especially IL-6 and TNF-α. Some clinical studies have shown the effect of RA on CYP metabolism. However, the effect of RA on the drug transporter OATP1B1 remains a gap.Methods: Patients with RA under pharmacological treatment (n = 10) and healthy volunteers (n = 15) treated for seven consecutive days with racemic fluvastatin (20, 40, or 80 mg/24 h) were investigated. Serial blood samples were collected during the last dose interval. All participants were assessed for cytokine profile and CYP2C9 genotype.Results: Patients with RA showed increased plasma concentrations of IFN-γ and TNF-α up to two and four times, respectively, when compared to healthy volunteers, whereas CYP2C9 activity based on genotype was considered normal or slightly reduced for both investigated groups. When compared to healthy volunteers, patients with RA presented higher values (median and 25th–75th percentiles) of normalized AUC for 20 mg dose (250 [114–405] vs. 96.7 [78.1–131] ng h mL−1 for (−)-3S,5R-fluvastatin and 163 [96.9–325] vs. 83.1 [61.7–107] ng⋅h⋅mL−1 for (+)-3R,5S-fluvastatin) and lower values of CL/F (40.9 [24.5–89.1] vs. 103 [75.9–128] L⋅h−1 for (−)-3S,5R-fluvastatin and 61.4 [30.6–103] vs. 120 [93.0–162] L⋅h−1 for (+)-3R,5S-fluvastatin) and V/F (73.0 [28.5–117] vs. 143 [108–221] L for (−)-3S,5R-fluvastatin and 93.9 [32.7–116] vs. 153 [122–234] L for (+)-3R,5S-fluvastatin) for both enantiomers.Conclusion: The lower values of CL/F and V/F for both fluvastatin enantiomers in RA patients suggest that the inflammatory disease downregulates the sinusoidal drug transporter OATP1B1, the rate-determining step in the hepatic clearance of fluvastatin. Rheumatoid arthritis OATP1B1 Fluvastatin Enantiomers Inflammation Benzi, Jhohann Richard de Lima verfasserin (orcid)0000-0001-6986-6193 aut de Souza, Flávio Falcão Lima verfasserin aut de Oliveira, Renê Donizeti Ribeiro verfasserin aut Donadi, Eduardo Antônio verfasserin aut Lanchote, Vera Lucia verfasserin (orcid)0000-0002-0074-4953 aut Enthalten in European journal of pharmaceutical sciences New York, NY [u.a.] : Elsevier, 1993 146 Online-Ressource (DE-627)300897308 (DE-600)1483522-8 (DE-576)094142033 1879-0720 nnns volume:146 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika AR 146
allfieldsSound	10.1016/j.ejps.2020.105264 doi (DE-627)ELV003827151 (ELSEVIER)S0928-0987(20)30053-1 DE-627 ger DE-627 rda eng 610 DE-600 15,3 ssgn PHARM DE-84 fid 44.40 bkl Caris, Juciene Aparecida verfasserin aut Rheumatoid arthritis downregulates the drug transporter OATP1B1: Fluvastatin as a probe 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Aims: Rheumatoid arthritis (RA) is a long term autoimmune inflammatory disease characterized by high autoantibody production and cytokine release, especially IL-6 and TNF-α. Some clinical studies have shown the effect of RA on CYP metabolism. However, the effect of RA on the drug transporter OATP1B1 remains a gap.Methods: Patients with RA under pharmacological treatment (n = 10) and healthy volunteers (n = 15) treated for seven consecutive days with racemic fluvastatin (20, 40, or 80 mg/24 h) were investigated. Serial blood samples were collected during the last dose interval. All participants were assessed for cytokine profile and CYP2C9 genotype.Results: Patients with RA showed increased plasma concentrations of IFN-γ and TNF-α up to two and four times, respectively, when compared to healthy volunteers, whereas CYP2C9 activity based on genotype was considered normal or slightly reduced for both investigated groups. When compared to healthy volunteers, patients with RA presented higher values (median and 25th–75th percentiles) of normalized AUC for 20 mg dose (250 [114–405] vs. 96.7 [78.1–131] ng h mL−1 for (−)-3S,5R-fluvastatin and 163 [96.9–325] vs. 83.1 [61.7–107] ng⋅h⋅mL−1 for (+)-3R,5S-fluvastatin) and lower values of CL/F (40.9 [24.5–89.1] vs. 103 [75.9–128] L⋅h−1 for (−)-3S,5R-fluvastatin and 61.4 [30.6–103] vs. 120 [93.0–162] L⋅h−1 for (+)-3R,5S-fluvastatin) and V/F (73.0 [28.5–117] vs. 143 [108–221] L for (−)-3S,5R-fluvastatin and 93.9 [32.7–116] vs. 153 [122–234] L for (+)-3R,5S-fluvastatin) for both enantiomers.Conclusion: The lower values of CL/F and V/F for both fluvastatin enantiomers in RA patients suggest that the inflammatory disease downregulates the sinusoidal drug transporter OATP1B1, the rate-determining step in the hepatic clearance of fluvastatin. Rheumatoid arthritis OATP1B1 Fluvastatin Enantiomers Inflammation Benzi, Jhohann Richard de Lima verfasserin (orcid)0000-0001-6986-6193 aut de Souza, Flávio Falcão Lima verfasserin aut de Oliveira, Renê Donizeti Ribeiro verfasserin aut Donadi, Eduardo Antônio verfasserin aut Lanchote, Vera Lucia verfasserin (orcid)0000-0002-0074-4953 aut Enthalten in European journal of pharmaceutical sciences New York, NY [u.a.] : Elsevier, 1993 146 Online-Ressource (DE-627)300897308 (DE-600)1483522-8 (DE-576)094142033 1879-0720 nnns volume:146 GBV_USEFLAG_U SYSFLAG_U GBV_ELV FID-PHARM SSG-OLC-PHA SSG-OPC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_187 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika AR 146
language	English
source	Enthalten in European journal of pharmaceutical sciences 146 volume:146
sourceStr	Enthalten in European journal of pharmaceutical sciences 146 volume:146
format_phy_str_mv	Article
bklname	Pharmazie Pharmazeutika
institution	findex.gbv.de
topic_facet	Rheumatoid arthritis OATP1B1 Fluvastatin Enantiomers Inflammation
dewey-raw	610
isfreeaccess_bool	false
container_title	European journal of pharmaceutical sciences
authorswithroles_txt_mv	Caris, Juciene Aparecida @@aut@@ Benzi, Jhohann Richard de Lima @@aut@@ de Souza, Flávio Falcão Lima @@aut@@ de Oliveira, Renê Donizeti Ribeiro @@aut@@ Donadi, Eduardo Antônio @@aut@@ Lanchote, Vera Lucia @@aut@@
publishDateDaySort_date	2020-01-01T00:00:00Z
hierarchy_top_id	300897308
dewey-sort	3610
id	ELV003827151
language_de	englisch
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Some clinical studies have shown the effect of RA on CYP metabolism. However, the effect of RA on the drug transporter OATP1B1 remains a gap.Methods: Patients with RA under pharmacological treatment (n = 10) and healthy volunteers (n = 15) treated for seven consecutive days with racemic fluvastatin (20, 40, or 80 mg/24 h) were investigated. Serial blood samples were collected during the last dose interval. All participants were assessed for cytokine profile and CYP2C9 genotype.Results: Patients with RA showed increased plasma concentrations of IFN-γ and TNF-α up to two and four times, respectively, when compared to healthy volunteers, whereas CYP2C9 activity based on genotype was considered normal or slightly reduced for both investigated groups. When compared to healthy volunteers, patients with RA presented higher values (median and 25th–75th percentiles) of normalized AUC for 20 mg dose (250 [114–405] vs. 96.7 [78.1–131] ng h mL−1 for (−)-3S,5R-fluvastatin and 163 [96.9–325] vs. 83.1 [61.7–107] ng⋅h⋅mL−1 for (+)-3R,5S-fluvastatin) and lower values of CL/F (40.9 [24.5–89.1] vs. 103 [75.9–128] L⋅h−1 for (−)-3S,5R-fluvastatin and 61.4 [30.6–103] vs. 120 [93.0–162] L⋅h−1 for (+)-3R,5S-fluvastatin) and V/F (73.0 [28.5–117] vs. 143 [108–221] L for (−)-3S,5R-fluvastatin and 93.9 [32.7–116] vs. 153 [122–234] L for (+)-3R,5S-fluvastatin) for both enantiomers.Conclusion: The lower values of CL/F and V/F for both fluvastatin enantiomers in RA patients suggest that the inflammatory disease downregulates the sinusoidal drug transporter OATP1B1, the rate-determining step in the hepatic clearance of fluvastatin.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Rheumatoid 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author	Caris, Juciene Aparecida
spellingShingle	Caris, Juciene Aparecida ddc 610 ssgn 15,3 fid PHARM bkl 44.40 misc Rheumatoid arthritis misc OATP1B1 misc Fluvastatin misc Enantiomers misc Inflammation Rheumatoid arthritis downregulates the drug transporter OATP1B1: Fluvastatin as a probe
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topic_title	610 DE-600 15,3 ssgn PHARM DE-84 fid 44.40 bkl Rheumatoid arthritis downregulates the drug transporter OATP1B1: Fluvastatin as a probe Rheumatoid arthritis OATP1B1 Fluvastatin Enantiomers Inflammation
topic	ddc 610 ssgn 15,3 fid PHARM bkl 44.40 misc Rheumatoid arthritis misc OATP1B1 misc Fluvastatin misc Enantiomers misc Inflammation
topic_unstemmed	ddc 610 ssgn 15,3 fid PHARM bkl 44.40 misc Rheumatoid arthritis misc OATP1B1 misc Fluvastatin misc Enantiomers misc Inflammation
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title	Rheumatoid arthritis downregulates the drug transporter OATP1B1: Fluvastatin as a probe
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title_full	Rheumatoid arthritis downregulates the drug transporter OATP1B1: Fluvastatin as a probe
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author_browse	Caris, Juciene Aparecida Benzi, Jhohann Richard de Lima de Souza, Flávio Falcão Lima de Oliveira, Renê Donizeti Ribeiro Donadi, Eduardo Antônio Lanchote, Vera Lucia
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author-letter	Caris, Juciene Aparecida
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title_sort	rheumatoid arthritis downregulates the drug transporter oatp1b1: fluvastatin as a probe
title_auth	Rheumatoid arthritis downregulates the drug transporter OATP1B1: Fluvastatin as a probe
abstract	Aims: Rheumatoid arthritis (RA) is a long term autoimmune inflammatory disease characterized by high autoantibody production and cytokine release, especially IL-6 and TNF-α. Some clinical studies have shown the effect of RA on CYP metabolism. However, the effect of RA on the drug transporter OATP1B1 remains a gap.Methods: Patients with RA under pharmacological treatment (n = 10) and healthy volunteers (n = 15) treated for seven consecutive days with racemic fluvastatin (20, 40, or 80 mg/24 h) were investigated. Serial blood samples were collected during the last dose interval. All participants were assessed for cytokine profile and CYP2C9 genotype.Results: Patients with RA showed increased plasma concentrations of IFN-γ and TNF-α up to two and four times, respectively, when compared to healthy volunteers, whereas CYP2C9 activity based on genotype was considered normal or slightly reduced for both investigated groups. When compared to healthy volunteers, patients with RA presented higher values (median and 25th–75th percentiles) of normalized AUC for 20 mg dose (250 [114–405] vs. 96.7 [78.1–131] ng h mL−1 for (−)-3S,5R-fluvastatin and 163 [96.9–325] vs. 83.1 [61.7–107] ng⋅h⋅mL−1 for (+)-3R,5S-fluvastatin) and lower values of CL/F (40.9 [24.5–89.1] vs. 103 [75.9–128] L⋅h−1 for (−)-3S,5R-fluvastatin and 61.4 [30.6–103] vs. 120 [93.0–162] L⋅h−1 for (+)-3R,5S-fluvastatin) and V/F (73.0 [28.5–117] vs. 143 [108–221] L for (−)-3S,5R-fluvastatin and 93.9 [32.7–116] vs. 153 [122–234] L for (+)-3R,5S-fluvastatin) for both enantiomers.Conclusion: The lower values of CL/F and V/F for both fluvastatin enantiomers in RA patients suggest that the inflammatory disease downregulates the sinusoidal drug transporter OATP1B1, the rate-determining step in the hepatic clearance of fluvastatin.
abstractGer	Aims: Rheumatoid arthritis (RA) is a long term autoimmune inflammatory disease characterized by high autoantibody production and cytokine release, especially IL-6 and TNF-α. Some clinical studies have shown the effect of RA on CYP metabolism. However, the effect of RA on the drug transporter OATP1B1 remains a gap.Methods: Patients with RA under pharmacological treatment (n = 10) and healthy volunteers (n = 15) treated for seven consecutive days with racemic fluvastatin (20, 40, or 80 mg/24 h) were investigated. Serial blood samples were collected during the last dose interval. All participants were assessed for cytokine profile and CYP2C9 genotype.Results: Patients with RA showed increased plasma concentrations of IFN-γ and TNF-α up to two and four times, respectively, when compared to healthy volunteers, whereas CYP2C9 activity based on genotype was considered normal or slightly reduced for both investigated groups. When compared to healthy volunteers, patients with RA presented higher values (median and 25th–75th percentiles) of normalized AUC for 20 mg dose (250 [114–405] vs. 96.7 [78.1–131] ng h mL−1 for (−)-3S,5R-fluvastatin and 163 [96.9–325] vs. 83.1 [61.7–107] ng⋅h⋅mL−1 for (+)-3R,5S-fluvastatin) and lower values of CL/F (40.9 [24.5–89.1] vs. 103 [75.9–128] L⋅h−1 for (−)-3S,5R-fluvastatin and 61.4 [30.6–103] vs. 120 [93.0–162] L⋅h−1 for (+)-3R,5S-fluvastatin) and V/F (73.0 [28.5–117] vs. 143 [108–221] L for (−)-3S,5R-fluvastatin and 93.9 [32.7–116] vs. 153 [122–234] L for (+)-3R,5S-fluvastatin) for both enantiomers.Conclusion: The lower values of CL/F and V/F for both fluvastatin enantiomers in RA patients suggest that the inflammatory disease downregulates the sinusoidal drug transporter OATP1B1, the rate-determining step in the hepatic clearance of fluvastatin.
abstract_unstemmed	Aims: Rheumatoid arthritis (RA) is a long term autoimmune inflammatory disease characterized by high autoantibody production and cytokine release, especially IL-6 and TNF-α. Some clinical studies have shown the effect of RA on CYP metabolism. However, the effect of RA on the drug transporter OATP1B1 remains a gap.Methods: Patients with RA under pharmacological treatment (n = 10) and healthy volunteers (n = 15) treated for seven consecutive days with racemic fluvastatin (20, 40, or 80 mg/24 h) were investigated. Serial blood samples were collected during the last dose interval. All participants were assessed for cytokine profile and CYP2C9 genotype.Results: Patients with RA showed increased plasma concentrations of IFN-γ and TNF-α up to two and four times, respectively, when compared to healthy volunteers, whereas CYP2C9 activity based on genotype was considered normal or slightly reduced for both investigated groups. When compared to healthy volunteers, patients with RA presented higher values (median and 25th–75th percentiles) of normalized AUC for 20 mg dose (250 [114–405] vs. 96.7 [78.1–131] ng h mL−1 for (−)-3S,5R-fluvastatin and 163 [96.9–325] vs. 83.1 [61.7–107] ng⋅h⋅mL−1 for (+)-3R,5S-fluvastatin) and lower values of CL/F (40.9 [24.5–89.1] vs. 103 [75.9–128] L⋅h−1 for (−)-3S,5R-fluvastatin and 61.4 [30.6–103] vs. 120 [93.0–162] L⋅h−1 for (+)-3R,5S-fluvastatin) and V/F (73.0 [28.5–117] vs. 143 [108–221] L for (−)-3S,5R-fluvastatin and 93.9 [32.7–116] vs. 153 [122–234] L for (+)-3R,5S-fluvastatin) for both enantiomers.Conclusion: The lower values of CL/F and V/F for both fluvastatin enantiomers in RA patients suggest that the inflammatory disease downregulates the sinusoidal drug transporter OATP1B1, the rate-determining step in the hepatic clearance of fluvastatin.
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title_short	Rheumatoid arthritis downregulates the drug transporter OATP1B1: Fluvastatin as a probe
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author2	Benzi, Jhohann Richard de Lima de Souza, Flávio Falcão Lima de Oliveira, Renê Donizeti Ribeiro Donadi, Eduardo Antônio Lanchote, Vera Lucia
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up_date	2024-07-06T20:55:23.693Z
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fullrecord_marcxml	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">ELV003827151</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230524151526.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230501s2020 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.ejps.2020.105264</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)ELV003827151</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(ELSEVIER)S0928-0987(20)30053-1</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rda</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="082" ind1="0" ind2="4"><subfield code="a">610</subfield><subfield code="q">DE-600</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">15,3</subfield><subfield code="2">ssgn</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">PHARM</subfield><subfield code="q">DE-84</subfield><subfield code="2">fid</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">44.40</subfield><subfield code="2">bkl</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Caris, Juciene Aparecida</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Rheumatoid arthritis downregulates the drug transporter OATP1B1: Fluvastatin as a probe</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2020</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">nicht spezifiziert</subfield><subfield code="b">zzz</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Aims: Rheumatoid arthritis (RA) is a long term autoimmune inflammatory disease characterized by high autoantibody production and cytokine release, especially IL-6 and TNF-α. Some clinical studies have shown the effect of RA on CYP metabolism. However, the effect of RA on the drug transporter OATP1B1 remains a gap.Methods: Patients with RA under pharmacological treatment (n = 10) and healthy volunteers (n = 15) treated for seven consecutive days with racemic fluvastatin (20, 40, or 80 mg/24 h) were investigated. Serial blood samples were collected during the last dose interval. All participants were assessed for cytokine profile and CYP2C9 genotype.Results: Patients with RA showed increased plasma concentrations of IFN-γ and TNF-α up to two and four times, respectively, when compared to healthy volunteers, whereas CYP2C9 activity based on genotype was considered normal or slightly reduced for both investigated groups. When compared to healthy volunteers, patients with RA presented higher values (median and 25th–75th percentiles) of normalized AUC for 20 mg dose (250 [114–405] vs. 96.7 [78.1–131] ng h mL−1 for (−)-3S,5R-fluvastatin and 163 [96.9–325] vs. 83.1 [61.7–107] ng⋅h⋅mL−1 for (+)-3R,5S-fluvastatin) and lower values of CL/F (40.9 [24.5–89.1] vs. 103 [75.9–128] L⋅h−1 for (−)-3S,5R-fluvastatin and 61.4 [30.6–103] vs. 120 [93.0–162] L⋅h−1 for (+)-3R,5S-fluvastatin) and V/F (73.0 [28.5–117] vs. 143 [108–221] L for (−)-3S,5R-fluvastatin and 93.9 [32.7–116] vs. 153 [122–234] L for (+)-3R,5S-fluvastatin) for both enantiomers.Conclusion: The lower values of CL/F and V/F for both fluvastatin enantiomers in RA patients suggest that the inflammatory disease downregulates the sinusoidal drug transporter OATP1B1, the rate-determining step in the hepatic clearance of fluvastatin.</subfield></datafield><datafield tag="650" ind1=" " ind2="4"><subfield code="a">Rheumatoid 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Rheumatoid arthritis downregulates the drug transporter OATP1B1: Fluvastatin as a probe

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