Intestinal absorption kinetics of a series of aminopenicillins and azidocillin. A comparative study in the rat.

Intestinal absorption rate constants of amoxicillin, ampicillin, epicillin, cyclacillin and azidocillin, by means of a static in situ intestinal perfusion method has been estimated. Luminal remaining antibiotic concentrations were determined using a standard microbiological technique. In order to establish statistically better absorption kinetics, five dose levels were used, ranging from 10 to 1000 micrograms/ml, and first order, Michaelis-Menten and combined first-order and Michaelis-Menten differential model equations were fitted to experimental data found for each antibiotic. According to the AIC test, the best equation for absorption kinetics was selected. Amoxicillin and ampicillin absorption mechanisms were better described by combined kinetics, while for cyclacillin and epicillin the most probable kinetics was that of Michaelis-Menten. For azidocillin, the only non-aminopenicillin component of this series, first order kinetics should be statistically selected.

Absorption kinetics of beta-alanine as model compound in rat small intestine.

Contradictory results have been reported on intestinal beta-alanine absorption, although a generalized view is that it could be a passive, nonmediated process. Since previous data from our laboratory suggested that some competition arises between intestinal absorption of the gamma-amino acidic drug baclofen and beta-alanine, a rat jejunum in situ study was undertaken in order to gain insight into the mechanism of beta-alanine absorption. Perfusion solutions with initial beta-alanine concentrations ranging from 0.3 to 56 mM were used. The beta-alanine absorption was clearly identified as a saturable process which obeys Michaelis-Menten equation kinetics, as assessed through two computer-assisted procedures based on differential and integrated forms of this equation. Parameter values found were: Vm = 3.88-4.72 mg.ml-1.h-1 (43.6-52.9 mM.h-1), and Km = 0.97-1.13 mg.ml-1 (10.9-12.7 mM). Statistical analysis does not account for the existence of significant parallel passive diffusion pathways (less than 0.2 h-1).