Nevirapine pharmacokinetics when initiated at 200 mg or 400 mg daily in HIV-1 and tuberculosis co-infected Ugandan adults on rifampicin

M Lamorde, P Byakika-Kibwika, V Okaba-Kayom, M Ryan, P Coakley, M Boffito, R Namakula, F Kalemeera, R Colebunders, D Back, S Khoo, C Merry

    Research output: Contribution to journalA1: Web of Science-article

    Abstract

    Background Rifampicin lowers nevirapine plasma concentrations by inducing cytochrome P450. However, few data are available on this interaction during the lead-in period of nevirapine treatment. Methods Eighteen HIV-1/tuberculosis co-infected adults receiving rifampicin daily as part of anti-tuberculosis therapy were evenly randomized to nevirapine initiation by dose escalation (NVP200) or nevirapine initiation at 200 mg twice daily (NVP400). Subjects underwent 12 h intensive pharmacokinetic sampling on Days 7, 14 and 21 of nevirapine treatment. A minimum effective concentration (MEC) of 3000 ng/mL was used to interpret nevirapine concentrations 12 h after dosing (C(12)). Trial registration number: NCT00617643 (www.clinicaltrials.gov). Results Day 7 geometric mean nevirapine C(12) [90% confidence interval (CI)] was 1504 (1127-2115) ng/mL and 3148 (2451-4687) ng/mL in the NVP200 and NVP400 arms, respectively (P < 0.01). Nevirapine C(12) on Days 14 and 21 was similar. On Day 21, nevirapine concentration in 64% of patients was below the MEC. On Day 7, geometric mean area under the curve (AUC(0-12)) was lower in the NVP200 arm, 25 223 (90% CI, 21 978-29 695) ng.h/mL versus 43 195 (35 607-57 035) ng.h/mL in the NVP400 arm (P < 0.01). Similarly, on Day 14, nevirapine AUC(0-12) was lower in the NVP200 arm 23 668 (18 253-32 218) ng.h/mL versus the NVP400 arm 44 918 (36 264-62 769) ng.h/mL (P = 0.03). Conclusions In co-treated patients, nevirapine concentrations were below the MEC during initiation with dose escalation. Nevirapine initiation at the maintenance dose of 200 mg twice daily is preferred. Sub-therapeutic nevirapine concentrations were common at Day 21 with either regimen. Evaluation of higher nevirapine maintenance doses may be considered.
    Original languageEnglish
    JournalJournal of Antimicrobial Chemotherapy
    Volume66
    Issue number1
    Pages (from-to)180-183
    Number of pages4
    ISSN0305-7453
    DOIs
    Publication statusPublished - 2011

    Keywords

    • B780-tropical-medicine
    • Viral diseases
    • HIV-1
    • AIDS
    • Co-infections
    • Bacterial diseases
    • Tuberculosis
    • Mycobacterium tuberculosis
    • HAART
    • Antiretrovirals
    • Nevirapine
    • Pharmacokinetics
    • Rifampicin
    • Dosage
    • Toxicity
    • Clinical trials
    • Uganda
    • Africa-East

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