Abstract

Background: Domperidone has long been used as a prokinetic agent in the treatment of epigastric distress symptoms. This study aimed to provide adequate evidence for registration approval of a new generic dry suspension formulation of domperidone by comparing the safety and pharmacokinetic profiles between the test and branded reference formulation in the context of fasted and fed condition.
Materials and methods: This was designed as a randomized, open-label, single-dose, two-period, two-treatment crossover study. 32 and 28 eligible healthy subjects were enrolled in the fasted and fed study, respectively. Each subject was randomly assigned to receive either the test or reference formulation in the first period, followed by a 1-week washout period and dosing of the alternate formulation in the second period. A series of blood samples were collected at scheduled timepoints within 48 hours after administration during each treatment period. Plasma concentrations of domperidone were determined by validated HPLC-MS/MS. Pharmacokinetic parameters, including C_max, t_max, AUC_0–t, AUC_0–∞, and T_1/2, were acquired based on the concentration vs. time profiles by non-compartmental analysis using WinNonlin software. Then the geometric mean ratios (GMR) of C_max, AUC_0–t, and AUC_0–∞ between the two formulations and corresponding 90% confidence intervals (CIs) were calculated for bioequivalence determination. Safety was assessed as routine.
Results: The two formulations showed similar pharmacokinetic profiles. Under fasted condition, the GMR and corresponding 90% CIs of AUC_0–t, AUC_0–∞, and C_max were 101.48% (96.79 – 106.38%), 101.17% (96.66 – 105.90%), and 104.61% (96.73 – 113.14%), respectively. Under fed condition, the GMR and corresponding 90% CIs were 105.46% (99.19 – 112.12%), 104.21% (98.19 – 110.61%), and 112.78% (103.64 – 122.73%), respectively, for AUC_0–t, AUC_0–∞, and C_max. All values fell within the accepted bioequivalence range of 80 – 125%. Both the test and the reference products were well tolerated without any serious or unexpected adverse reactions.
Conclusion: Pharmacokinetic bioequivalence was established between the two dry suspension formulations of domperidone in healthy Chinese subjects. Both products were safe and well tolerated.