The Clinical Pharmacokinetics of Pyrazinamide in HIV-Infected Persons with Tuberculosis

David C. Perlman, Yoninah Segal, Susan Rosenkranz, Petrie M. Rainey, Charles A. Peloquin, Rory P. Remmel, Keith Chirgwin, Nadim Salomon, Richard Hafner

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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.

Original languageEnglish (US)
Pages (from-to)556-564
Number of pages9
JournalClinical Infectious Diseases
Volume38
Issue number4
DOIs
StatePublished - Feb 15 2004

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Pyrazinamide
Tuberculosis
Pharmacokinetics
HIV
Drug Monitoring
Serum
Pharmaceutical Preparations

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Perlman, D. C., Segal, Y., Rosenkranz, S., Rainey, P. M., Peloquin, C. A., Remmel, R. P., ... Hafner, R. (2004). The Clinical Pharmacokinetics of Pyrazinamide in HIV-Infected Persons with Tuberculosis. Clinical Infectious Diseases, 38(4), 556-564. https://doi.org/10.1086/381096

The Clinical Pharmacokinetics of Pyrazinamide in HIV-Infected Persons with Tuberculosis. / Perlman, David C.; Segal, Yoninah; Rosenkranz, Susan; Rainey, Petrie M.; Peloquin, Charles A.; Remmel, Rory P.; Chirgwin, Keith; Salomon, Nadim; Hafner, Richard.

In: Clinical Infectious Diseases, Vol. 38, No. 4, 15.02.2004, p. 556-564.

Research output: Contribution to journalArticle

Perlman, DC, Segal, Y, Rosenkranz, S, Rainey, PM, Peloquin, CA, Remmel, RP, Chirgwin, K, Salomon, N & Hafner, R 2004, 'The Clinical Pharmacokinetics of Pyrazinamide in HIV-Infected Persons with Tuberculosis', Clinical Infectious Diseases, vol. 38, no. 4, pp. 556-564. https://doi.org/10.1086/381096
Perlman, David C. ; Segal, Yoninah ; Rosenkranz, Susan ; Rainey, Petrie M. ; Peloquin, Charles A. ; Remmel, Rory P. ; Chirgwin, Keith ; Salomon, Nadim ; Hafner, Richard. / The Clinical Pharmacokinetics of Pyrazinamide in HIV-Infected Persons with Tuberculosis. In: Clinical Infectious Diseases. 2004 ; Vol. 38, No. 4. pp. 556-564.
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