Pharmacokinetics, bioavailability, & bioequivalenceOriginal researchComparison of the Pharmacokinetics of a New 15-mg Modified-Release Tablet Formulation of Metoclopramide Versus a 10-mg Immediate-Release Tablet: A Single- and Multiple-Dose, Randomized, O

BackgroundMetoclopramide is a prokinetic and antiemetic agent.ObjectiveThe goal of this study was to assess the pharmacokinetics of a new, modified-release metoclopramide tablet and compare it with an immediate-release tablet to obtain marketing approval from the Mexican regulatory agency.MethodsThis was a single-center, randomized, open-label, parallel-group, single- and multiple-dose, pharmacokinetic study. Investigational products were administered to healthy Mexican male volunteers for 3 consecutive days: one 15-mg modified-release tablet every 12 hours or one 10-mg immediate-release tablet every 8 hours. Multiple blood samples were collected after the first and last doses of metoclopramide over a 24-hour period. Plasma metoclopramide concentrations were determined by using a validated HPLC method. Safety and tolerability were assessed by measurement of vital signs, clinical evaluations, and spontaneous reports from study subjects.ResultsAll 26 subjects were included in the analyses (mean [SD] age: 25 [6] years [range, 18-40 years]; body mass index, 23.44 [2.31] kg/m2 [range, 18.26-27.49 kg/m2]). Peak plasma concentrations were lower (Cmax, 33.13 [7.25] vs 46.04 [17.27] ng/mL after the first dose [P < 0.05]; Cmax,ss, 48.60 [8.52] vs 75.23 [21.27] ng/mL after the last dose [P < 0.05]) and occurred later (P < 0.05) with the modified-release formulation. In terms of average plasma concentrations (Cavgτ, 20.98 [3.94] vs 23.38 [7.35] ng/mL after the first dose; Cavg,ss, 22.20 [5.64] vs 23.02 [7.77] ng/mL after the last dose), differences did not reach the level of statistical significance (P > 0.05). Four adverse events were reported in the test group (abdominal distention [n = 2], epigastric pain [n = 1], and somnolence [n = 1]), and 3 were reported in the reference group (epigastric pain [n = 1], diarrhea [n = 1], and hiccups [n = 1]).ConclusionsThis study in a sample of selected healthy Mexican male volunteers suggests that the metoclopramide15-mg modified-release tablets have features compatible with the slow-release formulation (lower Cmax and longer Tmax) compared with immediate-release tablets.