Pharmacokinetics of pyrazinamide under fasting conditions, with food, and with antacids.
OBJECTIVE
To determine intrasubject and intersubject variability in, and the effects of food and antacids on, the pharmacokinetics of pyrazinamide (PZA).


METHODS
Randomized, four-period, crossover phase I study.


METHODS
Fourteen healthy men and women volunteers.


METHODS
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.


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.
Peloquin
C A
CA
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Bulpitt
A E
AE
Jaresko
G S
GS
Jelliffe
R W
RW
James
G T
GT
Nix
D E
DE
D000328:Adult; D000863:Antacids / Q000494:pharmacology*; D000995:Antitubercular Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D005215:Fasting; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011718:Pyrazinamide / Q000493:pharmacokinetics* / Q000494:pharmacology
D000863:Antacids; D000995:Antitubercular Agents; D011718:Pyrazinamide