No relationship between high nevirapine plasma concentration and hepatotoxicity in HIV-1-infected patients naive of antiretroviral treatment or switched from protease inhibitors.
OBJECTIVE
A prospective population pharmacokinetic study of nevirapine (NVP) was performed to test the relationship between hepatotoxicity and NVP trough plasma concentration and to identify which covariates could influence NVP pharmacokinetics.


METHODS
All patients [77 HIV-1 (human immunodeficiency virus type 1)-infected patients (128 samples)] were either on first-line antiretroviral therapy or switched from successful therapy containing protease inhibitor. Population pharmacokinetic parameters were estimated by a non-linear mixed-effect modelling method. Hepatotoxicity was evaluated by ASAT (aspartate aminotransferase) plasma level.


RESULTS
No correlation was found between high NVP trough plasma concentration and high ASAT level or the increase of ASAT level on NVP therapy. Age and Caucasian race were found to be significant covariates of NVP clearance (Cl/F). Population pharmacokinetic parameters (rate absorption constant=1.04 h(-1); Cl/F=3.31 h(-1); apparent volume of distribution=92 l) are consistent with previous studies.


CONCLUSIONS
High NVP trough plasma concentrations are not correlated with hepatotoxicity in our population. NVP clearance is decreased in the elderly patients, suggesting a potential increase of NVP plasma level and the interest of therapeutic drug monitoring for this population.
Dailly
Eric
E
Department of Pharmacology, Hôtel Dieu, 9 Quai Moncousu, 44093 Nantes cedex, France. eric.dailly@chu-nantes.fr
Billaud
Eric
E
Reliquet
Véronique
V
Breurec
Sébastien
S
Perré
Philippe
P
Léautez
Sophie
S
Jolliet
Pascale
P
Bourin
Michel
M
Raffi
François
F
D019380:Anti-HIV Agents / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D001219:Aspartate Aminotransferases / Q000097:blood; D001499:Bayes Theorem; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D015497:HIV-1; D006207:Half-Life; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D019829:Nevirapine / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*
D019380:Anti-HIV Agents; D019829:Nevirapine; D001219:Aspartate Aminotransferases