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Influence of darunavir coadministration on nevirapine pharmacokinetics in HIV‐infected patients: a population approach
Author(s) -
Dailly E,
Raffi F,
Perré P,
Martin J,
Deslandes G,
Jolliet P
Publication year - 2009
Publication title -
hiv medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 79
eISSN - 1468-1293
pISSN - 1464-2662
DOI - 10.1111/j.1468-1293.2009.00721.x
Subject(s) - nevirapine , darunavir , medicine , regimen , pharmacokinetics , pharmacology , population , nonmem , ritonavir , raltegravir , volume of distribution , reverse transcriptase inhibitor , human immunodeficiency virus (hiv) , viral load , virology , antiretroviral therapy , environmental health
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 using nonmem version 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.