Abstract
The pharmacokinetics of cefetamet pivoxil during administration of ascending oral doses were studied in 16 male normal healthy volunteers (age, 24.5 +/- 2.1 years; weight, 73.5 +/- 8.5 kg). The subjects were randomly assigned to four oral treatments of 500, 1,000, 1,500, and 2,000 mg of cefetamet pivoxil according to a four-by-four Latin square design. After an overnight fast, the drug was administered 10 min after a standard breakfast. It was found that both the rate and extent of prodrug absorption, measured as cefetamet adsorption, were reduced with increasing doses. The time to maximum concentration of cefetamet in serum was delayed from 4.00 +/- 0.81 to 4.88 +/- 0.96 h (P less than 0.05) when the dose of cefetamet pivoxil was increased from 500 to 2,000 mg. The dose-normalized values of area under the curve from 0 h to infinity for cefetamet and fraction of dose excreted as cefetamet were reduced by averages of 10.3 and 12.5%, respectively, over the dose range studied (P less than 0.05). The changes in rate and extent of prodrug absorption are thought to be the main factors contributing to the nonlinear relationship between maximum concentration in serum and dose. The change in absorption characteristics of cefetamet pivoxil with dose is, however, expected to have few clinical consequences because the magnitudes of these changes are comparable with their respective intragroup variations.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Blouin R. A., Kneer J., Stoeckel K. Pharmacokinetics of intravenous cefetamet (Ro 15-8074) and oral cefetamet pivoxil (Ro 15-8075) in young and elderly subjects. Antimicrob Agents Chemother. 1989 Mar;33(3):291–296. doi: 10.1128/aac.33.3.291. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koup J. R., Dubach U. C., Brandt R., Wyss R., Stoeckel K. Pharmacokinetics of cefetamet (Ro 15-8074) and cefetamet pivoxil (Ro 15-8075) after intravenous and oral doses in humans. Antimicrob Agents Chemother. 1988 Apr;32(4):573–579. doi: 10.1128/aac.32.4.573. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sommers D. K., van Wyk M., Moncrieff J., Schoeman H. S. Influence of food and reduced gastric acidity on the bioavailability of bacampicillin and cefuroxime axetil. Br J Clin Pharmacol. 1984 Oct;18(4):535–539. doi: 10.1111/j.1365-2125.1984.tb02501.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomson A. B., Pinchbeck B., Kirdeikis J., Kirdeikis P., Zuk L., Brunet M. K., Jurima-Romet M., Murray P. E. Evaluation of antacid tablets and liquid in fasting and fed men and women. Clin Ther. 1988;10(2):158–168. [PubMed] [Google Scholar]
- Welling P. G. How food and fluid affect drug absorption: results of initial studies. Postgrad Med. 1977 Jul;62(1):73–82. doi: 10.1080/00325481.1977.11712246. [DOI] [PubMed] [Google Scholar]
- Williams P. E., Harding S. M. The absolute bioavailability of oral cefuroxime axetil in male and female volunteers after fasting and after food. J Antimicrob Chemother. 1984 Feb;13(2):191–196. doi: 10.1093/jac/13.2.191. [DOI] [PubMed] [Google Scholar]
- Wise R., Andrews J. M., Piddock L. J. In vitro activity of Ro 15-8074 and Ro 19-5247, two orally administered cephalosporin metabolites. Antimicrob Agents Chemother. 1986 Jun;29(6):1067–1072. doi: 10.1128/aac.29.6.1067. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wyss R., Bucheli F. Determination of cefetamet and its orally active ester, cefetamet pivoxyl, in biological fluids by high-performance liquid chromatography. J Chromatogr. 1988 Aug 19;430(1):81–92. doi: 10.1016/s0378-4347(00)83136-9. [DOI] [PubMed] [Google Scholar]