In vivo / in vitro Correlation of Pharmacokinetics of Gentamicin, Vancomycin, Teicoplanin and Doripenem in a Bovine Blood Hemodialysis Model
Background: Elimination of a drug during renal replacement therapy is not only dependent on flow rates, molecular size and protein binding, but is often influenced by difficult to predict drug membrane interactions. In vitro models allow for extensive profiling of drug clearance using a wide array o...
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| Format: | Article |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.702455/full |
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| author | M G Vossen S Pferschy C Milacek M Haidinger Mario Karolyi Zoltan Vass Heinz Burgmann Alexandra Maier-Salamon S G Wicha W Jäger M Zeitlinger T Stimpfl T Wittek F Thalhammer |
| author_facet | M G Vossen S Pferschy C Milacek M Haidinger Mario Karolyi Zoltan Vass Heinz Burgmann Alexandra Maier-Salamon S G Wicha W Jäger M Zeitlinger T Stimpfl T Wittek F Thalhammer |
| author_sort | M G Vossen |
| collection | DOAJ |
| description | Background: Elimination of a drug during renal replacement therapy is not only dependent on flow rates, molecular size and protein binding, but is often influenced by difficult to predict drug membrane interactions. In vitro models allow for extensive profiling of drug clearance using a wide array of hemofilters and flow rates. We present a bovine blood based in vitro pharmacokinetic model for intermittent renal replacement therapy.Methods: Four different drugs were analyzed: gentamicin, doripenem, vancomicin and teicoplanin. The investigated drug was added to a bovine blood reservoir connected to a hemodialysis circuit. In total seven hemofilter models were analyzed using commonly employed flow rates. Pre-filter, post-filter and dialysate samples were drawn, plasmaseparated and analyzed using turbidimetric assays or HPLC. Protein binding of doripenem and vancomycin was measured in bovine plasma and compared to previously published values for human plasma.Results: Clearance values were heavily impacted by choice of membrane material and surface as well as by dialysis parameters such as blood flow rate. Gentamicin clearance ranged from a minimum of 90.12 ml/min in a Baxter CAHP-170 diacetate hemofilter up to a maximum of 187.90 ml/min in a Fresenius medical company Fx80 polysulfone model (blood flow rate 400 ml/min, dialysate flow rate 800 ml/min). Clearance of Gentamicin vs Vancomicin over the F80s hemofilter model using the same flow rates was 137.62 mL vs 103.25 ml/min. Doripenem clearance with the Fx80 was 141.25 ml/min.Conclusion: Clearance values corresponded very well to previously published data from clinical pharmacokinetic trials. In conjunction with in silico pharmacometric models. This model will allow precise dosing recommendations without the need of large scale clinical trials. |
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| id | doaj.art-f964f07fae8a4ef29aa69952c5d5f5c9 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-17T00:19:36Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-f964f07fae8a4ef29aa69952c5d5f5c92022-12-21T22:10:36ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-06-011210.3389/fphar.2021.702455702455In vivo / in vitro Correlation of Pharmacokinetics of Gentamicin, Vancomycin, Teicoplanin and Doripenem in a Bovine Blood Hemodialysis ModelM G Vossen0S Pferschy1C Milacek2M Haidinger3Mario Karolyi4Zoltan Vass5Heinz Burgmann6Alexandra Maier-Salamon7S G Wicha8W Jäger9M Zeitlinger10T Stimpfl11T Wittek12F Thalhammer13Clinical Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, Vienna, AustriaClinical Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, Vienna, AustriaClinical Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, Vienna, AustriaDepartment of Internal and Emergency Medicine, Bürgerspital Solothurn, Solothurn, SwitzerlandDepartment for Infectious Diseases, Sozialmedizinisches Zentrum Sued Kaiser-Franz-Josef-Spital, Wien, AustriaClinical Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, Vienna, AustriaClinical Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, Vienna, AustriaDepartment of Pharmaceutical Chemistry, Division of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, AustriaDepartment of Clinical Pharmacy, Institute of Pharmacy, University of Hamburg, Hamburg, GermanyDepartment of Pharmaceutical Chemistry, Division of Clinical Pharmacy and Diagnostics, University of Vienna, Vienna, AustriaDepartment of Clinical Pharmacology, Medical University of Vienna, Vienna, AustriaDepartment of Laboratory Medicine, Medical University of Vienna, Vienna, AustriaUniversity Clinic for Ruminants, University of Veterinary Medicine Vienna, Vienna, AustriaClinical Division of Infectious Diseases and Tropical Medicine, Department of Medicine I, Medical University of Vienna, Vienna, AustriaBackground: Elimination of a drug during renal replacement therapy is not only dependent on flow rates, molecular size and protein binding, but is often influenced by difficult to predict drug membrane interactions. In vitro models allow for extensive profiling of drug clearance using a wide array of hemofilters and flow rates. We present a bovine blood based in vitro pharmacokinetic model for intermittent renal replacement therapy.Methods: Four different drugs were analyzed: gentamicin, doripenem, vancomicin and teicoplanin. The investigated drug was added to a bovine blood reservoir connected to a hemodialysis circuit. In total seven hemofilter models were analyzed using commonly employed flow rates. Pre-filter, post-filter and dialysate samples were drawn, plasmaseparated and analyzed using turbidimetric assays or HPLC. Protein binding of doripenem and vancomycin was measured in bovine plasma and compared to previously published values for human plasma.Results: Clearance values were heavily impacted by choice of membrane material and surface as well as by dialysis parameters such as blood flow rate. Gentamicin clearance ranged from a minimum of 90.12 ml/min in a Baxter CAHP-170 diacetate hemofilter up to a maximum of 187.90 ml/min in a Fresenius medical company Fx80 polysulfone model (blood flow rate 400 ml/min, dialysate flow rate 800 ml/min). Clearance of Gentamicin vs Vancomicin over the F80s hemofilter model using the same flow rates was 137.62 mL vs 103.25 ml/min. Doripenem clearance with the Fx80 was 141.25 ml/min.Conclusion: Clearance values corresponded very well to previously published data from clinical pharmacokinetic trials. In conjunction with in silico pharmacometric models. This model will allow precise dosing recommendations without the need of large scale clinical trials.https://www.frontiersin.org/articles/10.3389/fphar.2021.702455/fullbovine bloodpharmacokineticschronic hemodialysisclearanceantimicrobial agent |
| spellingShingle | M G Vossen S Pferschy C Milacek M Haidinger Mario Karolyi Zoltan Vass Heinz Burgmann Alexandra Maier-Salamon S G Wicha W Jäger M Zeitlinger T Stimpfl T Wittek F Thalhammer In vivo / in vitro Correlation of Pharmacokinetics of Gentamicin, Vancomycin, Teicoplanin and Doripenem in a Bovine Blood Hemodialysis Model Frontiers in Pharmacology bovine blood pharmacokinetics chronic hemodialysis clearance antimicrobial agent |
| title | In vivo / in vitro Correlation of Pharmacokinetics of Gentamicin, Vancomycin, Teicoplanin and Doripenem in a Bovine Blood Hemodialysis Model |
| title_full | In vivo / in vitro Correlation of Pharmacokinetics of Gentamicin, Vancomycin, Teicoplanin and Doripenem in a Bovine Blood Hemodialysis Model |
| title_fullStr | In vivo / in vitro Correlation of Pharmacokinetics of Gentamicin, Vancomycin, Teicoplanin and Doripenem in a Bovine Blood Hemodialysis Model |
| title_full_unstemmed | In vivo / in vitro Correlation of Pharmacokinetics of Gentamicin, Vancomycin, Teicoplanin and Doripenem in a Bovine Blood Hemodialysis Model |
| title_short | In vivo / in vitro Correlation of Pharmacokinetics of Gentamicin, Vancomycin, Teicoplanin and Doripenem in a Bovine Blood Hemodialysis Model |
| title_sort | in vivo in vitro correlation of pharmacokinetics of gentamicin vancomycin teicoplanin and doripenem in a bovine blood hemodialysis model |
| topic | bovine blood pharmacokinetics chronic hemodialysis clearance antimicrobial agent |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.702455/full |
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