The Relationship between Nevirapine Plasma Concentrations and Abnormal Liver Function Tests

Abnormal liver function tests are frequently observed in HIV-infected individuals receiving nevirapine/ NVP (Viramune). In the present study, researchers investigate the relationship between total and unbound plasma concentrations of NVP and the liver enzymes alanine aminotransferase (ALT) and gamma-glutamyl transferase (gammaGT).

HIV-infected individuals [n = 85, 22 female, 34 hepatitis C or B virus (HCV or HBV(+))] receiving NVP (200 mg bd; median duration 66 weeks, range 3-189) and two nucleoside reverse transcriptase inhibitors (NRTIs) were enrolled into this study.

Blood samples were taken at C(trough) (12 hr postdose) for measurement of NVP and liver function tests (ALT and gammaGT). Plasma protein bound and unbound drug was separated using ultrafiltration and NVP concentrations quantified using HPLC-MS/MS.

A linear relationship was observed between total and unbound NVP C(trough)

(p < 0.0001). Patients with elevated ALT (>37 IU/liter; n = 31) had higher NVP unbound C(trough) than those with ALT within the normal range (p = 0.04) but there was no difference in total C(trough).

Logistic regression revealed no association between higher NVP C(trough) and ALT elevations. Significantly higher NVP total and unbound C(trough) were observed in patients with increased gammaGT.

Conclusions

Significantly higher unbound NVP C(trough) was observed in HCV/HBV(+) and on bivariate analysis, higher NVP C(trough) was associated with HCV/HBV coinfection .

The authors conclude, “Overall we found no strong association between NVP concentrations and hepatotoxicity. Although in this study NVP was well tolerated in HCV/HBV coinfected patients, higher plasma concentrations were observed.”

Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, UK.

08/18/04