Comparison of nevirapine plasma concentrations between lead-in and steady-state periods in Chinese HIV-infected patients.
OBJECTIVE
To investigate the potential of nevirapine 200 mg once-daily regimen and evaluate the influence of patient characteristics on nevirapine concentrations.


METHODS
This was a prospective, multicentre cohort study with 532 HIV-infected patients receiving nevirapine as a part of their initial antiretroviral therapy. Plasma samples were collected at trough or peak time at the end of week 2 (lead-in period) and week 4, 12, 24, 36, and 48 (steady-state period), and nevirapine concentrations were determined using a validated HPLC method. Potential influencing factors associated with nevirapine concentrations were evaluated using univariate and multivariate logistic regression.


RESULTS
A total of 2348 nevirapine plasma concentrations were collected, including 1510 trough and 838 peak values. The median nevirapine trough and peak concentration during the lead-in period were 4.26 µg/mL (IQR 3.05-5.61) and 5.07 µg/mL (IQR 3.92-6.44) respectively, which both exceeded the recommended thresholds of nevirapine plasma concentrations. Baseline hepatic function had a moderate effect on median nevirapine trough concentrations at week 2 (4.25 µg/mL v.s. 4.86 µg/mL, for ALT <1.5 × ULN and ≥ 1.5 × ULN, respectively, P = 0.045). No significant difference was observed in median nevirapine trough concentration between lead-in and steady-state periods in patients with baseline ALT and AST level ≥ 1.5 × ULN (P = 0.171, P = 0.769), which was different from the patients with ALT/AST level <1.5ULN. The median trough concentrations were significantly higher in HIV/HCV co-infected patients than those without HCV at week 48 (8.16 µg/mL v.s. 6.15 µg/mL, P = 0.004).


CONCLUSIONS
The 200 mg once-daily regimen of nevirapine might be comparable to twice-daily in plasma pharmacokinetics in Chinese population. Hepatic function prior to nevirapine treatment and HIV/HCV coinfection were significantly associated with nevirapine concentrations.
Department of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.
Huijuan
H
Kou
Xiaoli
X
Du
Yanling
Y
Li
Jing
J
Xie
Zhifeng
Z
Qiu
Min
M
Ye
Qiang
Q
Fu
Yang
Y
Han
Zhu
Z
Zhu
Taisheng
T
Li
D000293:Adolescent; D000368:Aged; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000097:blood*; D002681:China; D005260:Female; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D019829:Nevirapine / Q000008:administration & dosage / Q000097:blood*; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000097:blood*; D055815:Young Adult
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine