Influence of darunavir coadministration on nevirapine pharmacokinetics in HIV-infected patients: a population approach

Authors: Dailly, E; Raffi, F¹; Perré, P²; Martin, J³; Deslandes, G³; Jolliet, P

Source: HIV Medicine, Volume 10, Number 9, October 2009 , pp. 586-589(4)

Publisher: Wiley-Blackwell

Abstract:

Objective

The influence of ritonavir-boosted darunavir coadministration on nevirapine pharmacokinetics was investigated in HIV-infected patients using a population-based approach. Methods

The population was composed of 51 patients (89 samples; 42 patients treated with an antiretroviral regimen containing nevirapine and nucleoside/nucleotide reverse transcriptase inhibitors and nine patients treated with a regimen containing a combination of nevirapine and darunavir). A one-compartment model with first-order absorption was fitted to the data usingnonmemversion V (GloboMax, Ellicott City, MD, USA). Results

Relationships were established between nevirapine clearance (Cl) and age (Cl/F=2.42+47.2/age, where F denotes bioavailability) and between nevirapine volume of distribution (V_d) and the presence of darunavir in the antiretroviral regimen [V_d/F=38.0+75.0 (1 - darunavir coadministration), where darunavir coadministration is 1 for patients treated with a combination of nevirapine and darunavir and 0 for other patients]. According to this final model, a significant decrease in the means of Cl/F (3.84 ± 0.92 vs. 2.76 ± 1.00 L/h; P<0.05) and V_d/F (93.2 ± 31.10 vs. 39.8 ± 6.97 L; P<0.0001) and an increase in the mean of nevirapine trough plasma concentrations (3.68 ± 1.69 vs. 5.35 ± 3.20 mg/L; P<0.05) are observed if nevirapine is used in combination with darunavir. Conclusions

These results suggest that nevirapine exposure is increased when nevirapine is administered in combination with darunavir and that therapeutic drug monitoring of nevirapine should be performed if this antiretroviral regimen is considered.

Keywords: darunavir; nevirapine; pharmacokinetics

Document Type: Short communication

DOI: http://dx.doi.org/10.1111/j.1468-1293.2009.00721.x

Affiliations: 1: Infectious Diseases Department, Nantes University Hospital, Nantes, France and 2: Department of Medicine, La Roche sur Yon Hospital, La Roche sur Yon, France 3: Clinical Pharmacology Department, Nantes University Hospital, Nantes, France,

Publication date: 2009-10-01

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• In this Subject: Allergy & Immunology ,  Internal Medicine ,  Pediatrics
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