No Relationship Between High Nevirapine Plasma Concentration and Hepatotoxicity in Treatment-naïve HIV Patients or in Those Switched from Protease Inhibitors

A prospective population pharmacokinetic study of nevirapine/NVP (Viramune) was performed to test the relationship between hepatotoxicity and NVP trough plasma concentration and to identify which covariates could influence NVP pharmacokinetics.

All patients [77 HIV-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 are consistent with previous studies.

Conclusions

The authors conclude:

• High NVP trough plasma concentrations are not correlated with hepatotoxicity in this 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.

Department of Pharmacology, Hotel Dieu, Nantes, France.

06/04/04