Combined Recirculatory-compartmental Population Pharmacokinetic Modeling of Arterial and Venous Plasma S(+) and R(-) Ketamine Concentrations

Anesthesiology
Thomas K HenthornE Olofsen

Abstract

WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: The pharmacokinetics of infused drugs have been modeled without regard for recirculatory or mixing kinetics. We used a unique ketamine dataset with simultaneous arterial and venous blood sampling, during and after separate S(+) and R(-) ketamine infusions, to develop a simplified recirculatory model of arterial and venous plasma drug concentrations. S(+) or R(-) ketamine was infused over 30 min on two occasions to 10 healthy male volunteers. Frequent, simultaneous arterial and forearm venous blood samples were obtained for up to 11 h. A multicompartmental pharmacokinetic model with front-end arterial mixing and venous blood components was developed using nonlinear mixed effects analyses. A three-compartment base pharmacokinetic model with additional arterial mixing and arm venous compartments and with shared S(+)/R(-) distribution kinetics proved superior to standard compartmental modeling approaches. Total pharmacokinetic flow was estimated to be 7.59 ± 0.36 l/min (mean ± standard error of the estimate), and S(+) and R(-) elimination clearances were 1.23 ± 0.04 and 1.06 ± 0.03 l/min, respectively. The arm-tissue link rate constant was 0.18 ± 0.01 min, and the fraction of arm...Continue Reading

References

May 1, 1993·Journal of Biomedical Engineering·Y Plusquellec, G Houin
Apr 12, 1996·Journal of Chromatography. B, Biomedical Applications·J O Svensson, L L Gustafsson
Sep 4, 1999·Anesthesia and Analgesia·T C Krejcie, M J Avram
Nov 24, 2001·Clinical Pharmacology and Therapeutics·H IhmsenJ Schüttler
Jan 5, 2002·Journal of Pharmacokinetics and Pharmacodynamics·S L Beal
Jul 20, 2002·The Journal of Pharmacology and Experimental Therapeutics·Michael J AvramThomas K Henthorn
Oct 25, 2003·Anesthesiology·Michael J Avram, Tom C Krejcie
Jul 20, 2010·European Journal of Pain : EJP·Albert DahanElise Sarton
Aug 21, 2012·Journal of Pharmacokinetics and Pharmacodynamics·Richard N UptonLars Popper
Mar 1, 2015·European Journal of Clinical Pharmacology·Samuel FantaEija Kalso
Mar 2, 2018·Anesthesiology·Torsten BirkholzChristian Jeleazcov

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Citations

Oct 1, 2020·Anesthesiology·Jasper KampUNKNOWN Ketamine Pharmacokinetic Study Group
Feb 13, 2021·European Journal of Clinical Pharmacology·M E OttoMichiel J van Esdonk
May 31, 2021·Current Opinion in Anaesthesiology·Sabine Himmelseher, Eberhard F Kochs
Dec 30, 2021·Anesthesiology·Thomas K HenthornMichael J Avram

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