Metoclopramide modifies oral cephalexin pharmacokinetics in dogs

The purpose of this study was to investigate whether previous administration of metoclopramide affects cephalexin pharmacokinetics after its oral administration in dogs as well as whether these changes impair its predicted clinical efficacy. Six healthy beagle dogs were included in this study. Oral 25 mg/kg cephalexin monohydrate and intravenous 0.5 mg/kg metoclopramide HCl single doses were administered. Each dog received cephalexin or cephalexin following metoclopramide, with a 2-week washout period. Plasma concentrations of cephalexin were determined by microbiological assay. Cephalexin peak plasma concentration and area under the curve from 0 to infinity significantly increased from 18.77+/-2.8 microg/mL and 82.65+/-10.4 microg.h/mL to 21.88+/-0.8 microg/mL and 113.10+/-20.9 microg.h/mL, respectively, after pretreatment with metoclopramide. No differences between treatments were found for other pharmacokinetic parameters. Pharmacokinetic/pharmacodynamic indices calculated for highly susceptible staphylococci were similar for both experiences. Metoclopramide pretreatment may have increased cephalexin absorption by affecting its delivery to the intestine, and/or enhancing intestinal transporter PEPT1 function. Neither difference in the efficacy of cephalexin nor an increase in toxicity is expected as a result of this modification. Consequently, no dose adjustment is required in cephalexin-treated patients pretreated with metoclopramide.