Pharmacokinetic/pharmacodynamic modelling to describe the cholesterol lowering effect of rosuvastatin in people living with HIV. Clinical Pharmacokinetics
Courlet et al. aimed to characterise the pharmacokinetic profile of rosuvastatin and to describe the relationship between different rosuvastatin concentrations and non-high-density (HDL) cholesterol levels in people living with HIV using model-based simulations.
Participants of the Swiss HIV Cohort Study receiving rosuvastatin – a commonly prescribed lipid-lowering drug – were identified in Lausanne and Basel. Serial blood samples at predefined time points after rosuvastatin intake, as well as at unselected times at routine cohort visits were collected. Authors developed a pharmacokinetic model to assess the impact of demographic and clinical covariates on rosuvastatin disposition, and combined the model with serum lipid data (pharmacokinetic/pharmacodynamic model) to estimate the relationship between rosuvastatin plasma concentrations and non-HDL cholesterol levels.
The study included 65 patients (providing 154 rosuvastatin concentrations), 12% were women with a median age of 55 years (IQR 49-64). Median weight was 75 kg (66-85) and the median estimated glomerular filtration rate was 87 mL/min (79-119). Ritonavir-boosted darunavir was the most common antiretroviral drug administered together with rosuvastatin. In the multivariable pharmacokinetic model, authors detected high between-subject variability. No clinical or demographic covariate showed a significant influence on rosuvastatin absorption or clearance. Based on the pharmacokinetic/pharmacodynamic model simulations, coadministration with boosted protease inhibitors was not associated with differences in rosuvastatin AUC, but led to a 29% increase in rosuvastatin Cmax. The non-HDL cholesterol target of 2.8 mmol/L (according to the European AIDS Clinical Society guidelines) was met in 44% of individuals with 10mg rosuvastatin per day, and in 64% of individuals with 20mg daily.
In summary, the present study provides a useful model to describe the real-life relationship between rosuvastatin pharmacokinetics and its impact on non-HDL cholesterol among people living with HIV. The study findings support current guidelines, which recommend the same maximum dose of rosuvastatin in all individuals, irrespective of the use of boosted protease inhibitors.