Changes in nevirapine plasma concentrations over time and its relationship with liver enzyme elevations.
Liver enzyme elevations are frequently seen in patients treated with nevirapine (NVP). Both elevated NVP plasma levels and hepatitis C virus (HCV) infection seem to favor the development of NVP-related liver toxicity. We have examined variation on NVP C(trough) over time, as well as the impact of NVP C(trough) concentrations and the role of chronic hepatitis C on the incidence of liver enzyme elevations over a 48-week study period in HIV-infected patients on NVP therapy. Thirty-seven patients who initiated a triple regimen of NVP (200 mg bid) plus two nucleoside reverse transcriptase inhibitors (NRTI) were analyzed. A significant increase in serum transaminase levels occurred progressively over time. However, no significant variations in NVP plasma C(trough) were noticed in 48 weeks. In total population, maximum fold increase (MFI) in serum AST, ALT, and GGT was correlated with 24 week NVP C(trough). In HCV+ subjects, 12-week NVP C(trough) was closely correlated with maximum transaminase elevations, whereas in HCV- patients, 24-week concentrations were correlated with maximum transaminase increase. However, no differences in either NVP plasma C(trough) or in MFI in transaminase levels could be determined when comparing patients with and without hepatitis C at any time point.
Pharmacology Unit, Hospital Carlos III, Madrid, Spain. danifarre@hotmail.com
Daniel González
DG
De Requena
Inmaculada
I
Jiménez-Nácher
Vincent
V
Soriano
D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy* / Q000821:virology; D019698:Hepatitis C, Chronic / Q000150:complications*; D006801:Humans; D008099:Liver / Q000201:enzymology; D008107:Liver Diseases / Q000097:blood; D008297:Male; D019829:Nevirapine / Q000009:adverse effects* / Q000097:blood; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000097:blood
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase