Pharmacokinetics of pyrazinamide under fasting conditions, with food, and with antacids

Pharmacotherapy. 1998 Nov-Dec;18(6):1205-11.

Abstract

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 Cmax 53.4+/-10.4 microg/ml, Tmax 1.43+/-1.06 hours, and AUC(0-infinity) 673+/-79.7 microg x hr/ml. Fasting results are similar to those in previous reports. In the presence of antacids, subjects had a mean Cmax of 55.6+/-9.0 microg/ml, Tmax of 1.43+/-1.23 hours, and AUC(0-infinity) of 628+/-88.4 microg x hr/ml. In the presence of the high-fat meal, mean Cmax was 45.6+/-9.44 pg/ml, Tmax 3.09+/-1.74 hours, and AUC(0-infinity) 687+/-116 microg x hr/ml.

Conclusions: These small changes in Cmax, Tmax, and AUC(0-infinity) can be avoided by giving PZA on an empty stomach whenever possible.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase I
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Antacids / pharmacology*
  • Antitubercular Agents / pharmacokinetics*
  • Antitubercular Agents / pharmacology
  • Area Under Curve
  • Cross-Over Studies
  • Data Interpretation, Statistical
  • Fasting
  • Female
  • Food-Drug Interactions*
  • Humans
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Pyrazinamide / pharmacokinetics*
  • Pyrazinamide / pharmacology

Substances

  • Antacids
  • Antitubercular Agents
  • Pyrazinamide