Manel Aouri(1), Monia Guidi(2,6), Marga Rotger(3), Catalina Barcelo(3), Matthias Cavassini(4), Andri Rauch(5), Thierry Buclin(2), Laurent A. Decosterd(1), Amalio Telenti(3), Chantal Csajka(2,6), and the Swiss HIV Cohort Study.
(1)Innovation & Development, Laboratory of Clinical Pharmacology, Service of Biomedicine, University Hospital and University of Lausanne, Lausanne, Switzerland, (2)Division of Clinical Pharmacology, University Hospital Center, University of Lausanne, Lausanne, Switzerland, (3)Institute of Microbiology, University Hospital Center, University of Lausanne, Lausanne, Switzerland; (4)Division of Infectious Diseases, University Hospital Center, University of Lausanne, (5)Division of Infectious Diseases, University Hospital and University of Bern, Bern, Switzerland; (6)School of Pharmacy, Department of Pharmaceutical Sciences, University of Geneva, University of Lausanne Geneva, Switzerland.
Background. Rilpivirine (RPV), the latest non nucleoside reverse transcriptase inhibitor (NNRTI) active against HIV-1, is prescribed in single pill regimen at 25 mg once a day in combination with emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF). The aim of this observational study was to asses RPV pharmacokinetic profile, to quantify interpatient variability and to identify potential demographic and environmental factors that could influence drug exposure in HIV positive patients.
Methods. RPV concentrations data were collected from HIV patients as part of routine therapeutic drug monitoring performed in our hospital. A population PK analysis was performed with NONMEM® by comparing various structural models and the impacts of demographic factors (body weight and age) on RPV disposition.
Results. A total of 163 plasma concentrations were measured in 141 HIV-positive patients. A one-compartment model with zero-order absorption best characterized RPV pharmacokinetics. Average RPV CL was 11.9 (L/h) (CV 20.3%), volume of distribution 285 L, and mean absorption time 4.5h. None of the recorded demographic covariates showed an influence on rilpivirine pharmacokinetics.
Conclusion. The variability in RPV pharmacokinetics appears lower than for other NNRTIs. Under the standard regimen of 25 mg per day, some patients present concentrations below the cut-off value of 50 ng/ml recently proposed as target under standard dosing regimen1 but would remain above 12 ng/mL, an alternate target value derived from protein-adjusted in vitro data2. Further analyses are in progress to evaluate the influences of genetic polymorphisms, as well as other factors such as CYP-interfering comedications and clinical characteristics on RPV pharmacokinetics and to better characterize patients at risk of below therapeutic target exposure.
References:
[1]. Yapa H, et al. Pharmacokinetics (PK) of tenofovir (TFV), emtricitabine (FTC), and rilpivirine (RPV) over 10 days following drug cessation. EACS 2013 16-19th october, Brussels, Belgium.
[2]. Eviplera®. 2013. EMA Assessment report http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/002312/WC500158840.pdf
Reference: PAGE 23 () Abstr 3242 [www.page-meeting.org/?abstract=3242]
Poster: Drug/Disease modeling - Infection