INTRODUCTION: Darunavir is a second-generation protease inhibitor and is registered for the treatment of human immunodeficiency virus (HIV) -1 infection. The aim of this study was to develop and validate a darunavir population pharmacokinetic model based on data from daily practice.
METHODS: Datasets were obtained from two hospitals: ASST Fatebenefratelli Sacco University Hospital, Italy (hospital A) and University Medical Center Groningen, The Netherlands (hospital B). A pharmacokinetic model was developed using data from the largest dataset using the iterative two-stage Bayesian procedure within the MWPharm software package. External validation was conducted using data from the smaller dataset with Passing-Bablok regression and Bland-Altman analyses.
RESULTS: In total, data from 198 patients from hospital A and 170 patients from hospital B were eligible for inclusion. A one-compartment model with first-order absorption and elimination resulted in the best model. The Passing-Bablok analysis demonstrated a linear correlation between measured concentration and predicted concentration with r = 0.97 (p<0.05). The predicted values correlated well with the measured values as determined by a Bland-Altman analysis and were overestimated by a mean value of 0.12 mg/L (range 0.23-0.94 mg/L). 98.2% of the predicted values were within the limits of agreement.
CONCLUSION: A robust population pharmacokinetic model was developed which can support therapeutic drug monitoring of darunavir in daily outpatient settings.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.