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


BACKGROUND
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.
Research Department, Infectious Diseases Institute, Makerere University College of Health Sciences, Kampala, Uganda. mlamorde@idi.co.ug
Mohammed
M
Lamorde
Pauline
P
Byakika-Kibwika
Violet
V
Okaba-Kayom
Mairin
M
Ryan
Peter
P
Coakley
Marta
M
Boffito
Rhoda
R
Namakula
Francis
F
Kalemeera
Robert
R
Colebunders
David
D
Back
Saye
S
Khoo
Concepta
C
Merry
D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D019829:Nevirapine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010949:Plasma / Q000737:chemistry; D012293:Rifampin / Q000008:administration & dosage*; D013997:Time Factors; D014376:Tuberculosis / Q000188:drug therapy*; D014454:Uganda
D000900:Anti-Bacterial Agents; D019380:Anti-HIV Agents; D019829:Nevirapine; D012293:Rifampin