TY - JOUR
T1 - The Clinical Pharmacokinetics of Pyrazinamide in HIV-Infected Persons with Tuberculosis
AU - Perlman, David C.
AU - Segal, Yoninah
AU - Rosenkranz, Susan
AU - Rainey, Petrie M.
AU - Peloquin, Charles A.
AU - Remmel, Rory P.
AU - Chirgwin, Keith
AU - Salomon, Nadim
AU - Hafner, Richard
N1 - Funding Information:
Financial support: National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group (grants 1U01AI46370, UO1A127673, A12015802, A6201, A1802, A5802, A2205, AO603, A5901, A1701, A2503, #IUO1A13844, PHS NCRR MO1 RR05096, and AI 38855).
PY - 2004/2/15
Y1 - 2004/2/15
N2 - 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.
AB - 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.
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U2 - 10.1086/381096
DO - 10.1086/381096
M3 - Article
C2 - 14765350
AN - SCOPUS:1342280361
SN - 1058-4838
VL - 38
SP - 556
EP - 564
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 4
ER -
