Population pharmacokinetic/pharmacogenetic model of lopinavir/ritonavir in HIV-infected patients

Personalized Medicine
Elena López AspirozMaría José García Sánchez

Abstract

This study aims to develop a population pharmacokinetic/pharmacogenetic model for lopinavir/ritonavir (LPV/r) in European HIV-infected patients. A total of 693 LPV/r plasma concentrations were assessed and 15 single-nucleotide polymorphisms were genotyped. The population pharmacokinetic/pharmacogenetic model was created using a nonlinear mixed-effect approach (NONMEM® v.7.2.0., ICON Development Solutions, Dublin, Ireland). Covariates significantly related to LPV/r apparent clearance (CL/F) were ritonavir trough concentration (RTC), BMI, high-density lipoprotein cholesterol (HDL-C) and certain single-nucleotide polymorphisms in genes encoding for metabolizing enzymes, which are representable as follows: CL/F = (0.216BMI + 0.0125HDL-C) × 0.713RTC × 1.26rs28371764[C/T] × 0.528rs6945984[C/C] × 0.302 CYP3A4[1461insA/del] Conclusion: The LPV/r standard dose appears to be appropriate for the rs28371764[C/T] genotype. However, lower doses should be recommended for the rs6945984[C/C] and CYP3A4[1461insA/del] genotypes and even for those patients without any of these variants, as the standard dose seems to be higher than that which is required in order to achieve therapeutic levels.

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Citations

Oct 23, 2018·Basic & Clinical Pharmacology & Toxicology·Wan-Jie NiuLi-Jun Zhang
May 1, 2014·Personalized Medicine·Elena López AspirozThe Tormes Team

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Methods Mentioned

BETA
GAM
genotyping

Software Mentioned

NONMEM )
ADVAN2
Microsoft Developer Studio
NONMEM
SPSS
GAM
TRANS2
Xpose

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