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No relationship between high nevirapine plasma concentration and hepatotoxicity in HIV-1-infected patients naive of antiretroviral treatment or switched from protease inhibitors

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

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.

Conclusion

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.

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Acknowledgement

The authors thank Boehringer Ingelheim Pharmaceuticals Inc for their support in providing nevirapine.

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Authors and Affiliations

  1. Department of Pharmacology, Hôtel Dieu, Nantes, France

    Eric Dailly, Pascale Jolliet & Michel Bourin

  2. Nantes reference center for HIV disease, Hôtel Dieu, Nantes, France

    Eric Billaud, Véronique Reliquet, Sébastien Breurec & François Raffi

  3. Department of Medicine, La Roche sur Yon Hospital, La Roche sur Yon, France

    Philippe Perré & Sophie Léautez

  4. Laboratoire de Pharmacologie clinique, Hôtel Dieu, 9 Quai Moncousu, 44093 , Nantes Cedex, France

    Eric Dailly

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  1. Eric Dailly
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  2. Eric Billaud
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  3. Véronique Reliquet
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  4. Sébastien Breurec
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  5. Philippe Perré
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  6. Sophie Léautez
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  7. Pascale Jolliet
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  8. Michel Bourin
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  9. François Raffi
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Correspondence to Eric Dailly.

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Dailly, E., Billaud, E., Reliquet, V. et al. No relationship between high nevirapine plasma concentration and hepatotoxicity in HIV-1-infected patients naive of antiretroviral treatment or switched from protease inhibitors. Eur J Clin Pharmacol 60, 343–348 (2004). https://doi.org/10.1007/s00228-004-0769-5

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  • DOI: https://doi.org/10.1007/s00228-004-0769-5

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