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David C. Perlman, Yoninah Segal, Susan Rosenkranz, Petrie M. Rainey, Charles A. Peloquin, Rory P. Remmel, Keith Chirgwin, Nadim Salomon, Richard Hafner, for the ACTG 309 Team, The Clinical Pharmacokinetics of Pyrazinamide in HIV-Infected Persons with Tuberculosis, Clinical Infectious Diseases, Volume 38, Issue 4, 15 February 2004, Pages 556–564, https://doi.org/10.1086/381096
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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.
