Influence of antacid and ranitidine on the pharmacokinetics of oral cefetamet pivoxil.
The purpose of this investigation was to assess the influence that treatment with antacid and ranitidine had on the pharmacokinetics of oral cefetamet pivoxil in 18 healthy male volunteers. Each subject received, in an open-labeled, randomized, three-way crossover design, a single oral dose of 1,000 mg (two tablets) of cefetamet pivoxil 10 min after a standard breakfast during each of the following treatments: treatment A, control period; treatment B, antacid (80 ml of suspension; Maalox 70) administered on the evening before cefetamet pivoxil dosing (-12.5 h) and again 2 h before and 2 h after a standard breakfast; treatment C, ranitidine (150 mg) administered twice a day for 4 days and again 1 h and 10 min prior to cefetamet pivoxil dosing. Plasma and urine samples were collected over a 24-h period following cefetamet pivoxil administration. Cefetamet was analyzed by high-performance liquid chromatography. Oral bioavailability parameters (area under the concentration-time curve from 0 to 12 h, area under the concentration-time curve from 0 h to infinity, time to maximum concentration of drug in plasma, and maximum concentration of drug in plasma) were obtained by noncompartmental techniques. The results showed that none of these bioavailability parameters was significantly (P greater than 0.05) affected by antacid or rantidine coadministration. A compartmental analysis showed no significant differences. In addition, the terminal elimination half-life and the fraction of cefetamet excreted unchanged in the urine was also not significantly (P greater than 0.05) affected by antacid or ranitidine exposure. Relatively wide intrasubject variability was observed for time to maximum concentration of drug in plasma and terminal elimination half-life in several of the 18 subjects studied. Although these irregularities did not appear to be strongly associated with a particular treatment, they increased in subjects in both the antacid and H2-receptor antagonist treatment groups compared with those in subjects in the control treatment group. We conclude that antacid and ranitidine treatment likely does not alter the bioavailability of oral cefetamet pivoxil.
Blouin
R A
RA
College of Pharmacy, University of Kentucky, Lexington 40536-0082.
Kneer
J
J
Ambros
R J
RJ
Stoeckel
K
K
D000284:Administration, Oral; D000328:Adult; D000536:Aluminum Hydroxide / Q000494:pharmacology*; D000863:Antacids / Q000494:pharmacology*; D001682:Biological Availability; D015296:Ceftizoxime / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004338:Drug Combinations; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D008276:Magnesium Hydroxide / Q000494:pharmacology*; D008297:Male; D011899:Ranitidine / Q000494:pharmacology*
D000863:Antacids; D004338:Drug Combinations; D006635:Histamine H2 Antagonists; C013591:aluminum hydroxide, magnesium hydroxide, drug combination; D000536:Aluminum Hydroxide; D011899:Ranitidine; D015296:Ceftizoxime; C047445:cefetamet pivoxyl; D008276:Magnesium Hydroxide