Bioeqivalence Assessment of Two Domperidone Tablet Formulations

Abstract

A randomized, single-dose, crossover study was conducted to assess the bioavailability of two domperidone (CAS 57808-66-9) tablet formulations, Domperidone^TM (test) and a commercially available original preparation (reference) under fasting conditions. A 10 mg dose of each formulation was administered to 36 healthy male volunteers with a one-week washout period, 17 blood samples were collected over 48 h, plasma concentrations of domperidone were analyzed by a locally validated LC-MS-MS assay, and the pharmacokinetic parameters were determined by the standard non-compartmen-tal method. Mean ± SD maximum concentration (C_max), time to reach maximum concentration (T_max), areas under the curve (AUC_0→t and AUC_0→∞), and elimination constant (K_el) were 17.13 ± 9.62 and 17.67 ± 7.97 ng/ml, 0.87 ± 0.58, and 0.89 ± 0.33 h, 73.12 ± 43.37 and 71.45 ± 35.41 ng · h/ml, 90.32 ± 48.55 and 87.08 ± 40.29 ng · h/ml, and 0.069 ± 0.046 and 0.068 ± 0.048 h⁻¹ for the test and reference formulation, respectively. The parametric 90% confidence intervals on the mean difference between log-transformed values of the two formulations were within the acceptable bioequiva-lence range for AUC_0->t (87.84 % to 109.60%), AUC_0→∞ (89.05% to 111.67%) and C_max (83.28% to 107.50%). ANOVA revealed significant subject's effect for AUC_0→t, AUC_0→∞, C_max, and t_1/2 with a ratio of the inter-subject to intra-subject coefficient of variation of 2.10, 1.55, 1.10, and 1.02, respectively. The results indicate that the two formulations are equivalent in relation to the extent and rate of absorption and confirm the previously reported marked intra-individual variations in the pharmacokinetics of domperidone.

Key words

CAS 57808-66-9 - Domperidone, bioavailability, bioequivalence, pharmacokinetics - Dopamine D₂ receptor antagonists, peripheral