Use of rats chronically cannulated in the jugular vein and the duodenum in pharmacokinetic studies. Effect of ether anesthesia on absorption of amoxicillin.

In order to be able to use unanesthetized rats in pharmacokinetic studies it is necessary to find methods of drug administration and repeated blood sampling that do not stress the animals and therefore avoid possible alterations in the pharmacokinetic parameters caused by stress. Two surgical procedures that permit chronic cannulation of the jugular vein and duodenum of the rat are described in this paper, and the influence of ether (CAS 60-29-7) anesthesia on the intestinal absorption of amoxicillin (CAS 26787-78-0) is evaluated. Amoxicillin (2.2 mg) was administered to the rats by the oral and intraduodenal routes. Intraduodenal administration was performed in conscious rats, whereas oral administration was performed under light and heavy ether anesthesia. In each animal, 10 blood samples were collected through the jugular cannula at fixed times after drug administration and the plasma antibiotic concentration was determined by a microbiological diffusion procedure, with Micrococcus luteus as the test organism. Plasma concentration versus time curves of amoxicillin after intraduodenal and oral administration under light anesthesia were similar, with a slight delay in the tmax value for the oral administration. However, after oral administration of amoxicillin to rats under heavy anesthesia, antibiotic absorption was very irregular, with a decreased Cmax value and an increased tmax value as compared with the other two administration methods. Furthermore, the amount of amoxicillin absorbed in rats given the drug under heavy anesthesia was smaller than in the other two groups. These results suggest that drugs can be administered to rats under light ether anaesthesia without altering their pharmacokinetic features, but heavy anaesthesia can significantly alter their absorption.