Comparison 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, open-label, parallel-group study in healthy Mexican male volunteers.
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Resumo
BACKGROUND
Metoclopramide is a prokinetic and antiemetic agent.
OBJECTIVE
The 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.
METHODS
This 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.
RESULTS
All 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/m(2) [range, 18.26-27.49 kg/m2]). Peak plasma concentrations were lower (C(max), 33.13 [7.25] vs 46.04 [17.27] ng/mL after the first dose [P < 0.05]; C(max,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 (C(avgτ), 20.98 [3.94] vs 23.38 [7.35] ng/mL after the first dose; C(avg,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]).
CONCLUSIONS
This 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 C(max) and longer T(max)) compared with immediate-release tablets.
