Models for time-varying covariates in population pharmacokinetic-pharmacodynamic analysis

British Journal of Clinical Pharmacology
Ulrika WählbyMats O Karlsson

Abstract

If appropriately accounted for in a pharmacokinetic (PK)-pharmacodynamic (PD) model, time-varying covariates can provide additional information to that obtained from time-constant covariates. The aim was to present and apply two models applicable to time-varying covariates that capture such additional information. The first model estimates different covariate-parameter relationships for within- and between-individual variation in covariate values, by splitting the standard covariate model into a baseline covariate (BCOV) effect and a difference from baseline covariate (DCOV) effect. The second model allows the magnitude of the covariate effect to vary between individuals, by inclusion of interindividual variability in the covariate effect. The models were applied to four previously analysed data sets. The models were applied to 10 covariate-parameter relationships and for three of these the first extended model resulted in a significant improvement of the fit. Even when this model did not improve the fit significantly, it provided useful information because the standard covariate model, which assumes within- and between-patient covariate relationships of the same magnitude, was only supported by the data in four cases. The incl...Continue Reading

References

Dec 1, 1993·Journal of Pharmacokinetics and Biopharmaceutics·M O Karlsson, L B Sheiner
Dec 1, 1996·Acta Paediatrica·J N van den Anker
Oct 9, 1998·British Journal of Clinical Pharmacology·M C RosarioH L Elliott
Aug 10, 2000·British Journal of Clinical Pharmacology·B J AndersonN H Holford
Jul 27, 2001·Journal of Pharmacokinetics and Pharmacodynamics·U WählbyM O Karlsson
May 16, 2002·Clinical Pharmacology and Therapeutics·Diane R MouldGraham Ross
Nov 27, 2002·Journal of Pharmacokinetics and Pharmacodynamics·Ulrika WählbyMats O Karlsson
Dec 19, 2002·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Lena E FribergMats O Karlsson
May 25, 2004·Antimicrobial Agents and Chemotherapy·Thomas J WalshNolan Wood

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Citations

Mar 14, 2014·Journal of Pharmacokinetics and Pharmacodynamics·Elin M Svensson, Mats O Karlsson
Mar 7, 2014·Journal of Pharmacokinetics and Pharmacodynamics·Stefanie Hennig, Mats O Karlsson
May 10, 2012·Journal of Pharmaceutical Sciences·Takehito YamamotoHiroshi Suzuki
Dec 19, 2015·Journal of Pharmacokinetics and Pharmacodynamics·Anne-Gaëlle DosneMats O Karlsson
Jan 12, 2007·British Journal of Clinical Pharmacology·Reinier M van HestRon A Mathot
Feb 2, 2017·British Journal of Clinical Pharmacology·Elisabet StørsetAnders Åsberg
Apr 19, 2018·Pediatric Research·Lauren E KellyMartin Offringa
Sep 10, 2017·Journal of Pharmacokinetics and Pharmacodynamics·Anne-Gaëlle DosneMats O Karlsson
Dec 17, 2008·Clinical Pharmacology and Therapeutics·E HéninP Girard
Nov 12, 2019·CPT: Pharmacometrics & Systems Pharmacology·Kinjal SanghaviHeather E Vezina
Nov 12, 2019·CPT: Pharmacometrics & Systems Pharmacology·Jason ZhangLi Zhu
Oct 13, 2016·Journal of Pharmacokinetics and Pharmacodynamics·Anne-Gaëlle DosneMats O Karlsson
Oct 13, 2016·Journal of Pharmacokinetics and Pharmacodynamics·Anne-Gaëlle DosneMats O Karlsson
Mar 10, 2019·The AAPS Journal·Moustafa M A IbrahimMats O Karlsson
Jul 4, 2018·The AAPS Journal·Moustafa M A IbrahimMats O Karlsson
Jul 7, 2019·Advances in Therapy·Justin J WilkinsAkash Khandelwal
Oct 31, 2020·Clinical Pharmacokinetics·Perrine CourletUNKNOWN the Swiss HIV Cohort Study
Nov 19, 2021·The Journal of Antimicrobial Chemotherapy·Kim DaoMonia Guidi

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