Population pharmacokinetic modeling of the influence of chronic and acute biofilm-forming

We previously reported that ciprofloxacin (CIP) free lung interstitial concentrations are decreased by biofilm-forming Pseudomonas aeruginosa pulmonary chronic (14 d) infection. To get a better understanding on the influence of infection on CIP lung distribution, in the present study free lung inter...
Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Lock, Graziela De Araujo [verfasserIn] Helfer, Victória Etges [verfasserIn] Dias, Bruna Bernar [verfasserIn] Torres, Bruna Gaelzer Silva [verfasserIn] De Araújo, Bibiana Verlindo [verfasserIn] Dalla Costa, Teresa [verfasserIn]

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2023

Schlagwörter:	Ciprofloxacin Lung infection Epithelial lining fluid Microdialysis Population pharmacokinetic model

Übergeordnetes Werk:	Enthalten in: European journal of pharmaceutical sciences - New York, NY [u.a.] : Elsevier, 1993, 189
Übergeordnetes Werk:	volume:189

DOI / URN:	10.1016/j.ejps.2023.106546

Katalog-ID:	ELV062476181

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650		4	\|a Ciprofloxacin
650		4	\|a Lung infection
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700	1		\|a Dalla Costa, Teresa \|e verfasserin \|4 aut
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allfields	10.1016/j.ejps.2023.106546 doi (DE-627)ELV062476181 (ELSEVIER)S0928-0987(23)00176-8 DE-627 ger DE-627 rda eng 610 VZ 15,3 ssgn PHARM DE-84 fid 44.40 bkl Lock, Graziela De Araujo verfasserin aut Population pharmacokinetic modeling of the influence of chronic and acute biofilm-forming 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We previously reported that ciprofloxacin (CIP) free lung interstitial concentrations are decreased by biofilm-forming Pseudomonas aeruginosa pulmonary chronic (14 d) infection. To get a better understanding on the influence of infection on CIP lung distribution, in the present study free lung interstitial fluid and epithelial lining fluid (ELF) concentrations were determined by microdialysis in biofilm-forming P. aeruginosa acutely (2 d) and chronically infected (14 d) Wistar rats following CIP 20 mg/kg i.v. bolus dosing. A popPK model was developed, using NONMEM® (version 7.4.3) with FOCE+I, with plasma data described as a three-compartment model with first-order elimination. For lung data inclusion, the model was expanded to four compartments and ELF concentrations were described as a fraction of lung levels estimated as a distribution factor (ƒD). Acute infection had a minor impact on plasma and lung CIP distribution and both infection stages did not alter ELF drug penetration. Probability of target attainment of ƒAUC0–24/MIC ≥ 90 using 20 mg q8h, equivalent to 400 mg q8h in humans, showed that CIP free concentrations in plasma are adequate to successfully treat lung infections. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection. Ciprofloxacin Lung infection Epithelial lining fluid Microdialysis Population pharmacokinetic model Helfer, Victória Etges verfasserin aut Dias, Bruna Bernar verfasserin aut Torres, Bruna Gaelzer Silva verfasserin aut De Araújo, Bibiana Verlindo verfasserin aut Dalla Costa, Teresa verfasserin aut Enthalten in European journal of pharmaceutical sciences New York, NY [u.a.] : Elsevier, 1993 189 Online-Ressource (DE-627)300897308 (DE-600)1483522-8 (DE-576)094142033 1879-0720 nnns volume:189 GBV_USEFLAG_U GBV_ELV SYSFLAG_U 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2014 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika VZ AR 189
spelling	10.1016/j.ejps.2023.106546 doi (DE-627)ELV062476181 (ELSEVIER)S0928-0987(23)00176-8 DE-627 ger DE-627 rda eng 610 VZ 15,3 ssgn PHARM DE-84 fid 44.40 bkl Lock, Graziela De Araujo verfasserin aut Population pharmacokinetic modeling of the influence of chronic and acute biofilm-forming 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We previously reported that ciprofloxacin (CIP) free lung interstitial concentrations are decreased by biofilm-forming Pseudomonas aeruginosa pulmonary chronic (14 d) infection. To get a better understanding on the influence of infection on CIP lung distribution, in the present study free lung interstitial fluid and epithelial lining fluid (ELF) concentrations were determined by microdialysis in biofilm-forming P. aeruginosa acutely (2 d) and chronically infected (14 d) Wistar rats following CIP 20 mg/kg i.v. bolus dosing. A popPK model was developed, using NONMEM® (version 7.4.3) with FOCE+I, with plasma data described as a three-compartment model with first-order elimination. For lung data inclusion, the model was expanded to four compartments and ELF concentrations were described as a fraction of lung levels estimated as a distribution factor (ƒD). Acute infection had a minor impact on plasma and lung CIP distribution and both infection stages did not alter ELF drug penetration. Probability of target attainment of ƒAUC0–24/MIC ≥ 90 using 20 mg q8h, equivalent to 400 mg q8h in humans, showed that CIP free concentrations in plasma are adequate to successfully treat lung infections. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection. Ciprofloxacin Lung infection Epithelial lining fluid Microdialysis Population pharmacokinetic model Helfer, Victória Etges verfasserin aut Dias, Bruna Bernar verfasserin aut Torres, Bruna Gaelzer Silva verfasserin aut De Araújo, Bibiana Verlindo verfasserin aut Dalla Costa, Teresa verfasserin aut Enthalten in European journal of pharmaceutical sciences New York, NY [u.a.] : Elsevier, 1993 189 Online-Ressource (DE-627)300897308 (DE-600)1483522-8 (DE-576)094142033 1879-0720 nnns volume:189 GBV_USEFLAG_U GBV_ELV SYSFLAG_U 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2014 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika VZ AR 189
allfields_unstemmed	10.1016/j.ejps.2023.106546 doi (DE-627)ELV062476181 (ELSEVIER)S0928-0987(23)00176-8 DE-627 ger DE-627 rda eng 610 VZ 15,3 ssgn PHARM DE-84 fid 44.40 bkl Lock, Graziela De Araujo verfasserin aut Population pharmacokinetic modeling of the influence of chronic and acute biofilm-forming 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We previously reported that ciprofloxacin (CIP) free lung interstitial concentrations are decreased by biofilm-forming Pseudomonas aeruginosa pulmonary chronic (14 d) infection. To get a better understanding on the influence of infection on CIP lung distribution, in the present study free lung interstitial fluid and epithelial lining fluid (ELF) concentrations were determined by microdialysis in biofilm-forming P. aeruginosa acutely (2 d) and chronically infected (14 d) Wistar rats following CIP 20 mg/kg i.v. bolus dosing. A popPK model was developed, using NONMEM® (version 7.4.3) with FOCE+I, with plasma data described as a three-compartment model with first-order elimination. For lung data inclusion, the model was expanded to four compartments and ELF concentrations were described as a fraction of lung levels estimated as a distribution factor (ƒD). Acute infection had a minor impact on plasma and lung CIP distribution and both infection stages did not alter ELF drug penetration. Probability of target attainment of ƒAUC0–24/MIC ≥ 90 using 20 mg q8h, equivalent to 400 mg q8h in humans, showed that CIP free concentrations in plasma are adequate to successfully treat lung infections. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection. Ciprofloxacin Lung infection Epithelial lining fluid Microdialysis Population pharmacokinetic model Helfer, Victória Etges verfasserin aut Dias, Bruna Bernar verfasserin aut Torres, Bruna Gaelzer Silva verfasserin aut De Araújo, Bibiana Verlindo verfasserin aut Dalla Costa, Teresa verfasserin aut Enthalten in European journal of pharmaceutical sciences New York, NY [u.a.] : Elsevier, 1993 189 Online-Ressource (DE-627)300897308 (DE-600)1483522-8 (DE-576)094142033 1879-0720 nnns volume:189 GBV_USEFLAG_U GBV_ELV SYSFLAG_U 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2014 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika VZ AR 189
allfieldsGer	10.1016/j.ejps.2023.106546 doi (DE-627)ELV062476181 (ELSEVIER)S0928-0987(23)00176-8 DE-627 ger DE-627 rda eng 610 VZ 15,3 ssgn PHARM DE-84 fid 44.40 bkl Lock, Graziela De Araujo verfasserin aut Population pharmacokinetic modeling of the influence of chronic and acute biofilm-forming 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We previously reported that ciprofloxacin (CIP) free lung interstitial concentrations are decreased by biofilm-forming Pseudomonas aeruginosa pulmonary chronic (14 d) infection. To get a better understanding on the influence of infection on CIP lung distribution, in the present study free lung interstitial fluid and epithelial lining fluid (ELF) concentrations were determined by microdialysis in biofilm-forming P. aeruginosa acutely (2 d) and chronically infected (14 d) Wistar rats following CIP 20 mg/kg i.v. bolus dosing. A popPK model was developed, using NONMEM® (version 7.4.3) with FOCE+I, with plasma data described as a three-compartment model with first-order elimination. For lung data inclusion, the model was expanded to four compartments and ELF concentrations were described as a fraction of lung levels estimated as a distribution factor (ƒD). Acute infection had a minor impact on plasma and lung CIP distribution and both infection stages did not alter ELF drug penetration. Probability of target attainment of ƒAUC0–24/MIC ≥ 90 using 20 mg q8h, equivalent to 400 mg q8h in humans, showed that CIP free concentrations in plasma are adequate to successfully treat lung infections. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection. Ciprofloxacin Lung infection Epithelial lining fluid Microdialysis Population pharmacokinetic model Helfer, Victória Etges verfasserin aut Dias, Bruna Bernar verfasserin aut Torres, Bruna Gaelzer Silva verfasserin aut De Araújo, Bibiana Verlindo verfasserin aut Dalla Costa, Teresa verfasserin aut Enthalten in European journal of pharmaceutical sciences New York, NY [u.a.] : Elsevier, 1993 189 Online-Ressource (DE-627)300897308 (DE-600)1483522-8 (DE-576)094142033 1879-0720 nnns volume:189 GBV_USEFLAG_U GBV_ELV SYSFLAG_U 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2014 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika VZ AR 189
allfieldsSound	10.1016/j.ejps.2023.106546 doi (DE-627)ELV062476181 (ELSEVIER)S0928-0987(23)00176-8 DE-627 ger DE-627 rda eng 610 VZ 15,3 ssgn PHARM DE-84 fid 44.40 bkl Lock, Graziela De Araujo verfasserin aut Population pharmacokinetic modeling of the influence of chronic and acute biofilm-forming 2023 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier We previously reported that ciprofloxacin (CIP) free lung interstitial concentrations are decreased by biofilm-forming Pseudomonas aeruginosa pulmonary chronic (14 d) infection. To get a better understanding on the influence of infection on CIP lung distribution, in the present study free lung interstitial fluid and epithelial lining fluid (ELF) concentrations were determined by microdialysis in biofilm-forming P. aeruginosa acutely (2 d) and chronically infected (14 d) Wistar rats following CIP 20 mg/kg i.v. bolus dosing. A popPK model was developed, using NONMEM® (version 7.4.3) with FOCE+I, with plasma data described as a three-compartment model with first-order elimination. For lung data inclusion, the model was expanded to four compartments and ELF concentrations were described as a fraction of lung levels estimated as a distribution factor (ƒD). Acute infection had a minor impact on plasma and lung CIP distribution and both infection stages did not alter ELF drug penetration. Probability of target attainment of ƒAUC0–24/MIC ≥ 90 using 20 mg q8h, equivalent to 400 mg q8h in humans, showed that CIP free concentrations in plasma are adequate to successfully treat lung infections. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection. Ciprofloxacin Lung infection Epithelial lining fluid Microdialysis Population pharmacokinetic model Helfer, Victória Etges verfasserin aut Dias, Bruna Bernar verfasserin aut Torres, Bruna Gaelzer Silva verfasserin aut De Araújo, Bibiana Verlindo verfasserin aut Dalla Costa, Teresa verfasserin aut Enthalten in European journal of pharmaceutical sciences New York, NY [u.a.] : Elsevier, 1993 189 Online-Ressource (DE-627)300897308 (DE-600)1483522-8 (DE-576)094142033 1879-0720 nnns volume:189 GBV_USEFLAG_U GBV_ELV SYSFLAG_U 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2014 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700 44.40 Pharmazie Pharmazeutika VZ AR 189
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topic_facet	Ciprofloxacin Lung infection Epithelial lining fluid Microdialysis Population pharmacokinetic model
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authorswithroles_txt_mv	Lock, Graziela De Araujo @@aut@@ Helfer, Victória Etges @@aut@@ Dias, Bruna Bernar @@aut@@ Torres, Bruna Gaelzer Silva @@aut@@ De Araújo, Bibiana Verlindo @@aut@@ Dalla Costa, Teresa @@aut@@
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author	Lock, Graziela De Araujo
spellingShingle	Lock, Graziela De Araujo ddc 610 ssgn 15,3 fid PHARM bkl 44.40 misc Ciprofloxacin misc Lung infection misc Epithelial lining fluid misc Microdialysis misc Population pharmacokinetic model Population pharmacokinetic modeling of the influence of chronic and acute biofilm-forming
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topic_title	610 VZ 15,3 ssgn PHARM DE-84 fid 44.40 bkl Population pharmacokinetic modeling of the influence of chronic and acute biofilm-forming Ciprofloxacin Lung infection Epithelial lining fluid Microdialysis Population pharmacokinetic model
topic	ddc 610 ssgn 15,3 fid PHARM bkl 44.40 misc Ciprofloxacin misc Lung infection misc Epithelial lining fluid misc Microdialysis misc Population pharmacokinetic model
topic_unstemmed	ddc 610 ssgn 15,3 fid PHARM bkl 44.40 misc Ciprofloxacin misc Lung infection misc Epithelial lining fluid misc Microdialysis misc Population pharmacokinetic model
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title	Population pharmacokinetic modeling of the influence of chronic and acute biofilm-forming
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title_full	Population pharmacokinetic modeling of the influence of chronic and acute biofilm-forming
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author_browse	Lock, Graziela De Araujo Helfer, Victória Etges Dias, Bruna Bernar Torres, Bruna Gaelzer Silva De Araújo, Bibiana Verlindo Dalla Costa, Teresa
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title_sort	population pharmacokinetic modeling of the influence of chronic and acute biofilm-forming
title_auth	Population pharmacokinetic modeling of the influence of chronic and acute biofilm-forming
abstract	We previously reported that ciprofloxacin (CIP) free lung interstitial concentrations are decreased by biofilm-forming Pseudomonas aeruginosa pulmonary chronic (14 d) infection. To get a better understanding on the influence of infection on CIP lung distribution, in the present study free lung interstitial fluid and epithelial lining fluid (ELF) concentrations were determined by microdialysis in biofilm-forming P. aeruginosa acutely (2 d) and chronically infected (14 d) Wistar rats following CIP 20 mg/kg i.v. bolus dosing. A popPK model was developed, using NONMEM® (version 7.4.3) with FOCE+I, with plasma data described as a three-compartment model with first-order elimination. For lung data inclusion, the model was expanded to four compartments and ELF concentrations were described as a fraction of lung levels estimated as a distribution factor (ƒD). Acute infection had a minor impact on plasma and lung CIP distribution and both infection stages did not alter ELF drug penetration. Probability of target attainment of ƒAUC0–24/MIC ≥ 90 using 20 mg q8h, equivalent to 400 mg q8h in humans, showed that CIP free concentrations in plasma are adequate to successfully treat lung infections. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection.
abstractGer	We previously reported that ciprofloxacin (CIP) free lung interstitial concentrations are decreased by biofilm-forming Pseudomonas aeruginosa pulmonary chronic (14 d) infection. To get a better understanding on the influence of infection on CIP lung distribution, in the present study free lung interstitial fluid and epithelial lining fluid (ELF) concentrations were determined by microdialysis in biofilm-forming P. aeruginosa acutely (2 d) and chronically infected (14 d) Wistar rats following CIP 20 mg/kg i.v. bolus dosing. A popPK model was developed, using NONMEM® (version 7.4.3) with FOCE+I, with plasma data described as a three-compartment model with first-order elimination. For lung data inclusion, the model was expanded to four compartments and ELF concentrations were described as a fraction of lung levels estimated as a distribution factor (ƒD). Acute infection had a minor impact on plasma and lung CIP distribution and both infection stages did not alter ELF drug penetration. Probability of target attainment of ƒAUC0–24/MIC ≥ 90 using 20 mg q8h, equivalent to 400 mg q8h in humans, showed that CIP free concentrations in plasma are adequate to successfully treat lung infections. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection.
abstract_unstemmed	We previously reported that ciprofloxacin (CIP) free lung interstitial concentrations are decreased by biofilm-forming Pseudomonas aeruginosa pulmonary chronic (14 d) infection. To get a better understanding on the influence of infection on CIP lung distribution, in the present study free lung interstitial fluid and epithelial lining fluid (ELF) concentrations were determined by microdialysis in biofilm-forming P. aeruginosa acutely (2 d) and chronically infected (14 d) Wistar rats following CIP 20 mg/kg i.v. bolus dosing. A popPK model was developed, using NONMEM® (version 7.4.3) with FOCE+I, with plasma data described as a three-compartment model with first-order elimination. For lung data inclusion, the model was expanded to four compartments and ELF concentrations were described as a fraction of lung levels estimated as a distribution factor (ƒD). Acute infection had a minor impact on plasma and lung CIP distribution and both infection stages did not alter ELF drug penetration. Probability of target attainment of ƒAUC0–24/MIC ≥ 90 using 20 mg q8h, equivalent to 400 mg q8h in humans, showed that CIP free concentrations in plasma are adequate to successfully treat lung infections. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection. However, lung and ELF free interstitial concentrations might be insufficient to result in efficacious treatment of biofilm-forming P. aeruginosa chronic infection.
collection_details	GBV_USEFLAG_U GBV_ELV SYSFLAG_U 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_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2004 GBV_ILN_2014 GBV_ILN_2336 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 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_4338 GBV_ILN_4367 GBV_ILN_4700
title_short	Population pharmacokinetic modeling of the influence of chronic and acute biofilm-forming
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author2	Helfer, Victória Etges Dias, Bruna Bernar Torres, Bruna Gaelzer Silva De Araújo, Bibiana Verlindo Dalla Costa, Teresa
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doi_str	10.1016/j.ejps.2023.106546
up_date	2024-07-06T18:50:29.350Z
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Population pharmacokinetic modeling of the influence of chronic and acute biofilm-forming

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