ISSN:
1573-8744
Keywords:
absorption models
;
bioavailability
;
cefetamet
;
NONMEM
;
MKMODEL
;
population pharmacokinetics
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract Five absorption rate models have been compared for describing cefetamet data in 34 adults after oral administration of cefetamet pivoxil with food alone or in combination with either an antacid or an H2 antagonist. A sequential zero- then first-order input process provided the most flexible description of the absorption rate of cefetamet. If the first-order rate constant is linked to the zero- order input parameters the model can be interpreted as the consequence of solubility-limited absorption. While a sequential input is theoretically reasonable to assume, the first-order process appeared to be independent of the zero-order input. A population-based approach was applied to estimate the effect of dose and gastric pH increase on absorption and disposition. There appeared to be a dose-associated change in several parameters. The most marked change was an increase in volume of distribution of cefetamet. Treatments expected to increase gastric pH slowed the first-order component of the absorption process. Three models for estimating the extent of bioavailability have been compared using observations from 18 adults and 13 children receiving iv cefetamet and oral cefetamet pivoxil on two separate occasions. The most consistent estimates of the disposition parameters and the extent of bioavailability were achieved with the sequential zero- and first- order model under the assumption that steady slate volume of distribution and nonrenal clearance were the same after iv and oral treatment.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01061464
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