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Pharmacokinetics of Pyrazinamide under Fasting Conditions, with Food, and with Antacids
Author(s) -
Peloquin Charles A.,
Bulpitt Amy E.,
Jaresko George S.,
Jelliffe Roger W.,
James Gordon T.,
Nix David E.
Publication year - 1998
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1002/j.1875-9114.1998.tb03138.x
Subject(s) - pharmacokinetics , pyrazinamide , antacid , meal , crossover study , dose , medicine , postprandial , isoniazid , pharmacology , zoology , chemistry , gastroenterology , tuberculosis , placebo , biology , alternative medicine , pathology , insulin
Study Objectives . To determine intrasubject and intersubject variability in, and the effects of food and antacids on, the pharmacokinetics of pyrazinamide (PZA). Design . Randomized, four‐period, crossover phase I study. Subjects . Fourteen healthy men and women volunteers. Interventions . Subjects ingested single doses of PZA 30 mg/kg under fasting conditions twice, without a high‐fat meal and with an aluminum‐magnesium antacid. They also received standard dosages of isoniazid, rifampin, and ethambutol. Measurements and Main Results . Serum was collected for 48 hours and assayed by gas chromatography with mass selective detector. Data were analyzed by noncompartmental methods and a compartmental analysis using nonparametric expectation maximization. Both fasting conditions produced similar results: mean PZA C max 53.4 ± 10.4 μg/ml, T max 1.43 ± 1.06 hours, and AUC 0‐∞ , 673 ± 79.7 μg·hr/ml. Fasting results are similar to those in previous reports. In the presence of antacids, subjects had a mean C max of 55.6 ± 9.0 μg/ml, T max of 1.43 ± 1.23 hours, and AUC 0‐∞ of 628 ± 88.4 μg·hr/ml. In the presence of the high‐fat meal, mean C max was 45.6 ± 9.44 μg/ml, T max 3.09 ± 1.74 hours, and AUC 0‐∞ 687 ± 116 μg·hr/ml. Conclusions . These small changes in C max . T max , and AUC 0‐∞ . can be avoided by giving PZA on an empty stomach whenever possible. Conclusion : Serum concentrations in this study were consistent with those described previously. In addition, PZA's kinetic behavior was consistent between fasting treatments. Antacids and food had minimal effects on the agent's absorption. Samples drawn between 0.5 and 3 hours after dosing approached C max for most subjects, with 1 hour being closest. Samples drawn as early as day 2 of daily PZA therapy will produce serum concentrations that approach steady‐state values.