Pharmacokinetic/Pharmacodynamic Modelling to Describe the Cholesterol Lowering Effect of Rosuvastatin in People Living with HIV.

Details

Serval ID
serval:BIB_CF76FDD25628
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Pharmacokinetic/Pharmacodynamic Modelling to Describe the Cholesterol Lowering Effect of Rosuvastatin in People Living with HIV.
Journal
Clinical pharmacokinetics
Author(s)
Courlet P., Guidi M., Alves Saldanha S., Stader F., Traytel A., Cavassini M., Stoeckle M., Buclin T., Marzolini C., Decosterd L.A., Csajka C.
Working group(s)
and the Swiss HIV Cohort Study
ISSN
1179-1926 (Electronic)
ISSN-L
0312-5963
Publication state
Published
Issued date
03/2021
Peer-reviewed
Oui
Volume
60
Number
3
Pages
379-390
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
Rosuvastatin is a lipid-lowering agent widely prescribed in people living with HIV, which is actively transported into the liver, making it a potential victim of drug-drug interactions with antiretroviral agents.
The aims of this study were to characterise the pharmacokinetic profile of rosuvastatin and to describe the relationship between rosuvastatin concentrations and non-high-density lipoprotein (HDL)-cholesterol levels in people living with HIV.
A population pharmacokinetic model (NONMEM) was developed to quantify the influence of demographics, clinical characteristics and comedications on rosuvastatin pharmacokinetics. This model was combined with an indirect effect model to describe non-HDL-cholesterol measurements.
A two-compartment model with sequential zero- and first-order absorption best fitted the 154 rosuvastatin concentrations provided by 65 people living with HIV. None of the tested covariates significantly influenced rosuvastatin pharmacokinetics. A total of 403 non-HDL cholesterol values were available for pharmacokinetic-pharmacodynamic modelling. Baseline non-HDL cholesterol decreased by 14% and increased by 12% with etravirine and antiretroviral drugs with a known impact on the lipid profile (i.e. protease inhibitors, efavirenz, cobicistat), respectively. The baseline value was surprisingly 43% lower in people living with HIV aged 80 years compared with those aged 40 years. Simulations based on the covariate-free model predicted that, under standard rosuvastatin dosages of 5 mg and 20 mg once daily, 31% and 64% of people living with HIV would achieve non-HDL-cholesterol targets, respectively.
The high between-subject variability that characterises both rosuvastatin pharmacokinetic and pharmacodynamic profiles remained unexplained after the inclusion of usual covariates. Considering its limited potential for drug-drug interactions with antiretroviral agents and its potent lipid-lowering effect, rosuvastatin prescription appears safe and effective in people living with HIV with hypercholesterolaemia.
NCT03515772.
Pubmed
Web of science
Open Access
Yes
Create date
09/11/2020 11:30
Last modification date
16/03/2021 7:25
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