Abstract
The pharmacokinetics of intravenous (i.v.) cefetamet and the bioavailability of oral cefetamet pivoxil in infants aged 3.5 to 17.3 months who were hospitalized for urological surgery were characterized. The absorption of cefetamet pivoxil administered in a syrup formulation was 38 +/- 19% (n = 5) for infants, which was comparable to values observed for children and adults. The plasma half-life of i.v. cefetamet was 3.03 +/- 0.96 h (mean +/- standard deviation; n = 20) in the infants. This was not different from the value observed for normal adult subjects but was longer than that reported for children aged 3 to 12 years. Urinary recovery of cefetamet after i.v. administration to infants was 63.4 +/- 17.7% (n = 16), which was less than the 80% recovery found in older children and adults. The steady-state volume of distribution was 399 +/- 116 ml/kg of body weight. It was comparable in size and showed the same dependence on body weight as it did in children and adults. The mean systemic clearance per kilogram of body weight in the infants was lower than that in children and adults, apparently because of immaturity of clearance processes. A model that accounted for maturation and growth with increasing age was developed for the clearance. On the basis of this model, the clearance capacity increased from birth to 5 years by a factor of 4.5 because of maturation. Maturation progressed exponentially, with a half-life of 14 months. This model was used to develop dosing regimen guidelines for pediatric patients aged 3.5 months and older.
Full Text
The Full Text of this article is available as a PDF (247.3 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adolph E. F. Quantitative Relations in the Physiological Constitutions of Mammals. Science. 1949 Jun 10;109(2841):579–585. doi: 10.1126/science.109.2841.579. [DOI] [PubMed] [Google Scholar]
- Blouin R. A., Kneer J., Ambros R. J., Stoeckel K. Influence of antacid and ranitidine on the pharmacokinetics of oral cefetamet pivoxil. Antimicrob Agents Chemother. 1990 Sep;34(9):1744–1748. doi: 10.1128/aac.34.9.1744. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boxenbaum H. Interspecies scaling, allometry, physiological time, and the ground plan of pharmacokinetics. J Pharmacokinet Biopharm. 1982 Apr;10(2):201–227. doi: 10.1007/BF01062336. [DOI] [PubMed] [Google Scholar]
- Butler D. R., Kuhn R. J., Chandler M. H. Pharmacokinetics of anti-infective agents in paediatric patients. Clin Pharmacokinet. 1994 May;26(5):374–395. doi: 10.2165/00003088-199426050-00005. [DOI] [PubMed] [Google Scholar]
- Crom W. R. Pharmacokinetics in the child. Environ Health Perspect. 1994 Dec;102 (Suppl 11):111–117. doi: 10.1289/ehp.94102s11111. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ducharme M. P., Edwards D. J., McNamara P. J., Stoeckel K. Bioavailability of syrup and tablet formulations of cefetamet pivoxil. Antimicrob Agents Chemother. 1993 Dec;37(12):2706–2709. doi: 10.1128/aac.37.12.2706. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Edwards D. J., Stoeckel K. The pharmacokinetics of new oral cephalosporins in children. Chemotherapy. 1992;38 (Suppl 2):2–9. doi: 10.1159/000239090. [DOI] [PubMed] [Google Scholar]
- Gehan E. A., George S. L. Estimation of human body surface area from height and weight. Cancer Chemother Rep. 1970 Aug;54(4):225–235. [PubMed] [Google Scholar]
- Hayton W. L. Pharmacokinetic parameters for interspecies scaling using allometric techniques. Health Phys. 1989;57 (Suppl 1):159–164. doi: 10.1097/00004032-198907001-00020. [DOI] [PubMed] [Google Scholar]
- Hayton W. L., Stoeckel K. Age-associated changes in ceftriaxone pharmacokinetics. Clin Pharmacokinet. 1986 Jan-Feb;11(1):76–86. doi: 10.2165/00003088-198611010-00005. [DOI] [PubMed] [Google Scholar]
- Knoester P. D., Underberg W. J., Beijnen J. H. Clinical pharmacokinetics and pharmacodynamics of anticancer agents in pediatric patients (review). Anticancer Res. 1993 Sep-Oct;13(5C):1795–1808. [PubMed] [Google Scholar]
- Koff S. A., Peller P. A., Young D. C., Pollifrone D. L. The assessment of obstruction in the newborn with unilateral hydronephrosis by measuring the size of the opposite kidney. J Urol. 1994 Aug;152(2 Pt 2):596–599. doi: 10.1016/s0022-5347(17)32659-9. [DOI] [PubMed] [Google Scholar]
- Nahata M. C. Variability in clinical pharmacology of drugs in children. J Clin Pharm Ther. 1992 Dec;17(6):365–368. doi: 10.1111/j.1365-2710.1992.tb01319.x. [DOI] [PubMed] [Google Scholar]
- Reed M. D., Blumer J. L. Therapeutic drug monitoring in the pediatric intensive care unit. Pediatr Clin North Am. 1994 Dec;41(6):1227–1243. doi: 10.1016/s0031-3955(16)38870-8. [DOI] [PubMed] [Google Scholar]
- Stoeckel K., Hayton W. L., Edwards D. J. Clinical pharmacokinetics of oral cephalosporins. Antibiot Chemother (1971) 1995;47:34–71. doi: 10.1159/000430073. [DOI] [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]
