Comparison of the pharmacokinetics of a new 30 mg modified-release tablet formulation of metoclopramide for once-a-day administration versus 10 mg immediate-release tablets: a single and multiple-dose, randomized, open-label, parallel study in healthy male subjects

• Published in: European journal of drug metabolism and pharmacokinetics Vol. 37; no. 4; pp. 279 - 288
• Main Authors: Bernardo-Escudero, Roberto, Alonso-Campero, Rosalba, Francisco-Doce, María Teresa de Jesús, Cortés-Fuentes, Myriam, Villa-Vargas, Miriam, Ángeles-Uribe, Juan
• Format: Journal Article
• Language: English
• Published: Paris Springer-Verlag 01-12-2012
• Subjects: Adolescent; Adult; Antiemetics - pharmacokinetics; Biomedical and Life Sciences; Biomedicine; Chemistry, Pharmaceutical; Drug Administration Schedule; Human Physiology; Humans; Male; Medical Biochemistry; Metoclopramide - administration & dosage; Metoclopramide - adverse effects; Metoclopramide - pharmacokinetics; Middle Aged; Original Paper; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Pharmacy; Tablets; Modified-release; Healthy subjects; Immediate-release; Bioavailability; Pharmacokinetics; Metoclopramide
• ISSN: 0378-7966; 2107-0180
• DOI: 10.1007/s13318-012-0082-0

The study aimed to assess the pharmacokinetics of a new, modified-release metoclopramide tablet, and compare it to an immediate-release tablet. A single and multiple-dose, randomized, open-label, parallel, pharmacokinetic study was conducted. Investigational products were administered to 26 healthy Hispanic Mexican male volunteers for two consecutive days: either one 30 mg modified-release tablet every 24 h, or one 10 mg immediate-release tablet every 8 h. Blood samples were collected after the first and last doses of metoclopramide. Plasma metoclopramide concentrations were determined by high-performance liquid chromatography. Safety and tolerability were assessed through vital signs measurements, clinical evaluations, and spontaneous reports from study subjects. All 26 subjects were included in the analyses [mean (SD) age: 27 (8) years, range 18–50; BMI: 23.65 (2.22) kg/m
2
, range 18.01–27.47)]. Peak plasmatic concentrations were not statistically different with both formulations, but occurred significantly later (
p
 < 0.05) with the modified-release form [tmax: 3.15 (1.28) vs. 0.85 (0.32) h and tmax-ss: 2.92 (1.19) vs. 1.04 (0.43) h]. There was no difference noted in the average plasma concentrations [Cavgτ: 23.90 (7.90) vs. 20.64 (7.43) ng/mL after the first dose; and Cavg-ss: 31.14 (9.64) vs. 35.59 (12.29) ng/mL after the last dose, (
p
 > 0.05)]. One adverse event was reported in the test group (diarrhea), and one in the reference group (headache). This study suggests that the 30 mg modified-release metoclopramide tablets show features compatible with slow-release formulations when compared to immediate-release tablets, and is suitable for once-a-day administration.