Darunavir Population Pharmacokinetic Model Based on HIV Outpatient Data. Issue 1 (February 2019) - Daskapan, Alper
Abstract : Background: Darunavir is a second-generation protease inhibitor and is registered for the treatment of 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: Data sets were obtained from 2 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 data set using the iterative two-stage Bayesian procedure within the MWPharm software package. External validation was conducted using data from the smaller data set 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 1-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 2 = 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). A total of 98.2% of the predicted values were within the limits of agreement. Conclusions: A robust population pharmacokinetic model was developed, which can support therapeutic drug monitoring of darunavir in daily outpatient settings. Abstract : Supplemental Digital Content is Available in the Text.