{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T10:34:52Z","timestamp":1790418892194,"version":"4.1.0"},"reference-count":16,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2009,10,1]],"date-time":"2009-10-01T00:00:00Z","timestamp":1254355200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2009,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Nevirapine is a nonnucleoside reverse transcriptase inhibitor used as part of combination therapy for human immunodeficiency virus (HIV) infection. Nevirapine may be prescribed for patients with hepatic fibrosis and cirrhosis. Significant autoinduction of cytochrome P450 3A4 and 2B6 following multiple dosing prompted an assessment of the metabolic profiles in patients with liver disease receiving chronic nevirapine therapy. HIV-infected patients with hepatic fibrosis who were receiving a stable antiretroviral regimen containing nevirapine for \u22656 weeks had liver biopsy specimens assessed by Ishak histologic scoring and were grouped by severity (group 1, Ishak scores of 1 and 2; group 2, Ishak scores of 3 and 4; group 3, Ishak scores of 5 and 6). Steady-state trough nevirapine levels were determined for all patients, and additional measurements were obtained at 1, 2, and 4 h following nevirapine dosing for a subset of patients. The pharmacokinetics of nevirapine and its five metabolites were characterized, and a comparison of the results for the different Ishak groups was performed. Among 51 patients with hepatic fibrosis, the majority of whom were coinfected with hepatitis C virus or hepatitis B virus, differences between the maximum and the minimum observed plasma concentrations demonstrated a statistically significant flattening of the systemic exposure curves with progression from Ishak group 1 to Ishak group 2 or 3, suggesting a decrease in systemic clearance with the progression of liver disease. However, there were no significant differences in the trough and the maximum nevirapine concentrations between the Ishak groups. The metabolite profiles were also comparable across the Ishak groups. In HIV-infected patients who were chronically treated with nevirapine and who had various degrees of hepatic fibrosis, including cirrhosis, trough plasma nevirapine concentrations were not significantly increased, and thus, no dose adjustment is warranted.<\/jats:p>","DOI":"10.1128\/aac.00460-09","type":"journal-article","created":{"date-parts":[[2009,7,21]],"date-time":"2009-07-21T00:58:33Z","timestamp":1248137913000},"page":"4147-4152","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":13,"title":["Pharmacokinetic Assessment of Nevirapine and Metabolites in Human Immunodeficiency Virus Type 1-Infected Patients with Hepatic Fibrosis"],"prefix":"10.1128","volume":"53","author":[{"given":"Anna Maria","family":"Cammett","sequence":"first","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas R.","family":"MacGregor","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan M.","family":"Wruck","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franco","family":"Felizarta","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Miailhes","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josep","family":"Mallolas","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Piliero","sequence":"additional","affiliation":[{"name":"Boehringer Ingelheim Pharmaceuticals, Inc., Ridgefield, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/512086"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/524080"},{"key":"e_1_3_2_4_2","unstructured":"The HEPADOSE study: evaluation of protease inhibitors and non nucleoside analogue plasma concentrations in HIV\/HCV and HIV infected patients 2005"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.2174\/1389200043489054"},{"key":"e_1_3_2_6_2","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1002\/j.1875-9114.1995.tb02884.x","volume":"15","year":"1995","unstructured":"Figg, W. D., G. E. Dukes, H. R. Lesesne, S. W. Carson, S. S. Songer, J. F. Pritchard, D. J. Hermann, J. R. Powell, and L. J. Hak. 1995. Comparison of quantitative methods to assess hepatic function: Pugh's classification, indocyanine green, antipyrine, and dextromethorphan. Pharmacotherapy15:693-700.","journal-title":"Pharmacotherapy"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/0168-8278(95)80226-6"},{"key":"e_1_3_2_8_2","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1177\/135965350501000114","volume":"10","year":"2005","unstructured":"Kappelhoff, B. S., F. van Leth, T. R. MacGregor, J. Lange, J. H. Beijnen, and A. D. Huitema. 2005. Nevirapine and efavirenz pharmacokinetics and covariate analysis in the 2NN study. Antivir. Ther.10:145-155.","journal-title":"Antivir. Ther."},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1177\/135965350501000404","volume":"10","year":"2005","unstructured":"Kappelhoff, B. S., F. van Leth, P. A. Robinson, T. R. MacGregor, E. Baraldi, F. Montella, D. E. Uip, M. A. Thompson, D. B. Russell, J. M. Lange, J. H. Beijnen, and A. D. Huitema. 2005. Are adverse events of nevirapine and efavirenz related to plasma concentrations? Antivir. Ther.10:489-498.","journal-title":"Antivir. Ther."},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0009-9236(99)80079-4"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1099-081X(199909)20:6<285::AID-BDD187>3.0.CO;2-V"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002030-200403260-00007"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0731-7085(98)00312-4"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","first-page":"895","DOI":"10.1016\/S0090-9556(24)15239-7","volume":"27","year":"1999","unstructured":"Riska, P., M. Lamson, T. MacGregor, J. Sabo, S. Hattox, J. Pav, and J. Keirns. 1999. Disposition and biotransformation of the antiretroviral drug nevirapine in humans. Drug Metab. Dispos.27:895-901.","journal-title":"Drug Metab. 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