The clinical pharmacokinetics of pyrazinamide in HIV-infected persons with tuberculosis.
The pharmacokinetics of pyrazinamide (PZA) in patients with human immunodeficiency virus (HIV)-related tuberculosis are incompletely characterized. Serum PZA concentrations were determined at 2, 6, and 10 h after dosing in 48 subjects with HIV-related tuberculosis. Estimates of drug exposure using 2-h concentrations and 2- and 3-time point estimates of area under time-concentration curves (AUCs) were compared. For daily dosing, 2-h concentrations less than low and very low literature-defined cut points (i.e., 20 and 10 mg/L) were noted for 2 subjects (4%) and 1 subject (2%), respectively. For intermittent PZA dosing, 1 subject (4%) had a 2-h concentration that was less than the low cut point (25 mg/L). Correlations between 2-h concentration and AUC estimates based on 2- or 3-time point concentration determinations were strong. In HIV-infected persons receiving antituberculosis regimens containing PZA, lower-than-expected 2-h concentrations are uncommon. For therapeutic monitoring of PZA drug exposure, determination of a 2-h postdose concentration appears as reliable as 2- or 3-time point estimates of the AUC for PZA.
Perlman
David C
DC
Beth Israel Medical Center, New York, NY 10003, USA. dperlman@bethisraelny.org
Segal
Yoninah
Y
Rosenkranz
Susan
S
Rainey
Petrie M
PM
Peloquin
Charles A
CA
Remmel
Rory P
RP
Chirgwin
Keith
K
Salomon
Nadim
N
Hafner
Richard
R
D000328:Adult; D017677:Age Distribution; D000995:Antitubercular Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011718:Pyrazinamide / Q000097:blood / Q000493:pharmacokinetics*; D014376:Tuberculosis / Q000150:complications / Q000378:metabolism*
D000995:Antitubercular Agents; D011718:Pyrazinamide