PMID- 21316541
OWN - NLM
STAT- MEDLINE
DCOM- 20110527
LR  - 20131121
IS  - 1879-114X (Electronic)
IS  - 0149-2918 (Linking)
VI  - 32
IP  - 13
DP  - 2010 Dec
TI  - Relative bioavailability of two formulations of nevirapine 200-mg tablets in 
      healthy Chinese male volunteers: a single-dose, randomized-sequence, open-label, 
      two-way crossover study.
PG  - 2258-64
LID - 10.1016/S0149-2918(10)80028-1 [doi]
AB  - BACKGROUND: Nevirapine was the first member of the nonnucleoside reverse 
      transcriptase inhibitor class to be approved for the treatment of HIV infection. 
      It binds directly to the allosteric site on the reverse transcriptase and 
      inhibits the activity of both RNA- and DNA-dependent DNA polymerases. OBJECTIVE: 
      This study compared the pharmacokinetics and relative bioavailability of a test 
      and reference formulation of nevirapine 200-mg tablets after single oral doses in 
      healthy Chinese men to meet regulatory criteria for marketing of the new generic 
      formulation. METHODS: This single-dose, randomized-sequence, open-label, 2-way 
      crossover study was conducted at the Nanjing First Hospital of Nanjing Medical 
      University, Nanjing, China. Healthy male Chinese volunteers were randomized in a 
      1ratio1 ratio to receive a single 200-mg (3.2-mg/kg) tablet of the test or reference 
      formulation, followed by a 2-week washout period and administration of the 
      alternate formulation. The study drugs were administered after a 10-hour 
      overnight fast. Concentrations of nevirapine were assayed using an HPLC-UV 
      method. For analysis of nevirapine pharmacokinetic parameters, blood samples were 
      obtained before dosing and at regularly scheduled intervals over 168 hours after 
      administration. The 2 formulations would be assumed to be bioequivalent for 
      regulatory purposes if the 90% CIs for the log-transformed ratios of nevirapine 
      AUC and C(max) were within the range established by the US Food and Drug 
      Administration (0.80-1.25). Tolerability was evaluated throughout the study based 
      on vital signs, physical examinations, 12-lead ECGs, and subject interviews 
      concerning adverse events (AEs). RESULTS: Twenty Chinese male subjects were 
      enrolled in and completed the study. Their mean age was 23 years (range, 21-25 
      years), mean weight was 63 kg (range, 56-70 kg), and mean height was 171 cm 
      (range, 166-176 cm). No period or sequence effect was observed. The mean (SD) 
      t((1/2)) was 38.12 (2.23) hours for the test tablet and 36.79 (5.06) hours for the 
      reference tablet; T(max) was 3.1 (0.7) and 3.0 (0.7) hours, respectively; C(max) 
      was 2.52 (0.31) and 2.60 (0.48) mg . L(-1); AUC(0-168) was 155.66 (22.41) and 
      150.66 (22.11) mg . h . L(-1); and AUC(0-infinity) was 163.30 (22.88) and 157.75 (22.87) 
      mg . h . L(-1). Mean relative bioavailability was 103.6% (8.6%). The 90% CIs for 
      the log-transformed ratios of C(max) (93.51-102.13) and AUC(0-168) ( 
      99.84-106.74) were within the predetermined range for the assumption of 
      bioequivalence. One subject reported mild headache after receiving the test 
      formulation; the relationship of this AE to study drug was considered uncertain. 
      No serious or clinically significant AEs were observed or reported during the 
      study. CONCLUSIONS: In this single-dose study in healthy fasted Chinese males, 
      the test tablet met the regulatory criterion for assumption of bioequivalence to 
      the reference tablet. Both formulations were well tolerated in the population 
      studied. SFDA registration no: 2009L04358.
CI  - Copyright (c) 2010 Elsevier HS Journals, Inc. Published by EM Inc USA.. All rights 
      reserved.
FAU - Zhu, Yubing
AU  - Zhu Y
AD  - Department of Clinical Pharmacology, Nanjing First Hospital of Nanjing Medical 
      University, Nanjing, Jiangsu, China.
FAU - Zhang, Qian
AU  - Zhang Q
FAU - Yu, Cuixia
AU  - Yu C
FAU - Zou, Jianjun
AU  - Zou J
FAU - Yang, Xiaohong
AU  - Yang X
FAU - Hu, Yunfang
AU  - Hu Y
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PL  - United States
TA  - Clin Ther
JT  - Clinical therapeutics
JID - 7706726
RN  - 0 (Anti-HIV Agents)
RN  - 99DK7FVK1H (Nevirapine)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Anti-HIV Agents/administration & dosage/adverse effects/blood/*pharmacology
MH  - Biological Availability
MH  - Chemistry, Pharmaceutical
MH  - China
MH  - Chromatography, High Pressure Liquid
MH  - Cross-Over Studies
MH  - Humans
MH  - Male
MH  - Nevirapine/administration & dosage/adverse effects/blood/*pharmacokinetics
MH  - Young Adult
EDAT- 2011/02/15 06:00
MHDA- 2011/05/28 06:00
CRDT- 2011/02/15 06:00
PHST- 2010/10/18 00:00 [accepted]
PHST- 2011/02/15 06:00 [entrez]
PHST- 2011/02/15 06:00 [pubmed]
PHST- 2011/05/28 06:00 [medline]
AID - S0149-2918(10)80028-1 [pii]
AID - 10.1016/S0149-2918(10)80028-1 [doi]
PST - ppublish
SO  - Clin Ther. 2010 Dec;32(13):2258-64. doi: 10.1016/S0149-2918(10)80028-1.