Lack of interaction of metoclopramide on oral amoxicillin kinetics in dogs

Abstract

Amoxicillin is a beta-lactam antibiotic frequently used inveterinary medicine. Amoxicillin activity is time dependent, thatis death of bacteria is related to drug concentration and length oftime bacteria are exposed to the drug (Drusano, 2004; McKellaret al., 2004). Amoxicillin may be administered associated withother treatments, including antiemetic agents, giving raise topotential pharmacological interactions. We have proved in dogsthat the total exposure of oral cephalexin was enhanced whenthe antibiotic was administered after metoclopramide (Pradoset al., 2007). On the contrary, both the peak serum concentra-tion and the disposition curve of a prodrug of ceftizoxime werenot affected when the dogs were pretreated with this prokineticagent (Mori et al., 2001).The purpose of this study was to investigate whether previousadministration of metoclopramide affects amoxicillin pharmaco-kinetics after its oral administration to dogs as well as whetherthese changes impair its predicted clinical efficacy. In addition, asage-related changes may affect drugs disposition in geriatricpatients (Harvey & Paddleford, 1999; Dowling, 2005), two ageddogs were included in this study.The institutional animal use and care committee approved thestudy protocol. Five adult (age 5.0 ± 3.0 years) and two aged(15.0 years) beagle dogs received a single oral dose of 25 mg⁄kgamoxicillin trihydrate (500 mg⁄5 mL oral aqueous suspension,Amoxidal 500, Roemmers) with and without an intravenous0.5 mg⁄kg metoclopramide previous (20 min) treatment, with a2-week washout period between phases. The subjects were all ingood health, and none of the dogs had a history of allergy tobeta-lactamsorhadreceivedantibiotics4 weekspriortoenteringthe experience. Dogs were randomly assigned to treatment, andaged dogs were treated in opposite groups.Blood samples were collected from the jugular vein atpredetermined times up to 11.5 h postadministration. Plasmawas separated by centrifugation at 1500 g for 10 min and wasstored at 4 C until analysis within 72 h after collection.Amoxicillin concentrations were calculated by a microbiologicalprocedure (Bennet et al., 1966). Standard curves were preparedin canine plasma and run simultaneously with test samples. Thecalibration curve was linear over the concentration range tested(0.390–50 lg⁄mL, r