Evaluation of pharmacokinetics of metoclopramide administered via subcutaneous bolus and intravenous constant rate infusion to adult horses

ObjectiveTo determine the pharmacokinetics (PK) of metoclopramide administered via intravenous continuous rate infusion (IV CRI) and subcutaneous (SC) bolus and evaluate for gastrointestinal motility and adverse side effects.Study designExperimental study; randomized, crossover design.AnimalsSix healthy adult horses.MethodsEach horse received metoclopramide via IV CRI (0.04 mg/kg/h for 24 h) and SC bolus (0.08 mg/kg once), with >= 1 week washout period between. Plasma was analyzed by UPLC-MS/MS. Compartmental modeling was used to determine PK parameters for each treatment; nonparametric superposition was used to simulate multiple SC bolus regimens. Gastrointestinal motility and evidence of adverse effects were monitored.ResultsTmax (h) for SC bolus was 0.583 +/- 0.204 versus 17.3 +/- 6.41 for IV CRI, while Cmax (ng/mL) was 27.7 +/- 6.38 versus 43.6 +/- 9.97, respectively. AUC (h x ng/mL) was calculated as 902 +/- 189 for 24 h IV CRI versus 244 +/- 37.4 simulated for 0.08 mg/kg SC bolus every 8 h. Simulations revealed similar exposure between groups with administration of 0.96 mg/kg/day SC bolus, divided into three, four, or six doses. SC bolus bioavailability was estimated as 110 +/- 11.5%. No clear trends in motility alteration were identified. No adverse effects were noted.ConclusionRepeated SC boluses of metoclopramide at 0.08 mg/kg would result in lower total drug exposure and Tmax than IV CRI administration but would be highly bioavailable.Clinical significanceHigher and/or more frequent SC bolus doses are needed to achieve a similar AUC to IV CRI. No adverse effects were noted; however, evaluation of alternative dosing strategies is warranted.