title: The clinical pharmacokinetics of pyrazinamide in HIV-infected persons with tuberculosis.
abstract: 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.
authors.affiliation: Beth Israel Medical Center, New York, NY 10003, USA. dperlman@bethisraelny.org
authors.forename: David C
authors.initials: DC
authors.lastname: Perlman
authors.forename: Yoninah
authors.initials: Y
authors.lastname: Segal
authors.forename: Susan
authors.initials: S
authors.lastname: Rosenkranz
authors.forename: Petrie M
authors.initials: PM
authors.lastname: Rainey
authors.forename: Charles A
authors.initials: CA
authors.lastname: Peloquin
authors.forename: Rory P
authors.initials: RP
authors.lastname: Remmel
authors.forename: Keith
authors.initials: K
authors.lastname: Chirgwin
authors.forename: Nadim
authors.initials: N
authors.lastname: Salomon
authors.forename: Richard
authors.initials: R
authors.lastname: Hafner
mesh_terms: 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*
chemical_list: D000995:Antitubercular Agents; D011718:Pyrazinamide