Comparative pharmacokinetics and bioequivalence of two tablet formulations of 2 mg risperidone in healthy Thai male volunteers

Background: Risperidone is an atypical antipsychotic drug with potent serotonin and moderate dopamine antagonistic properties. It possesses good bioavailability following oral administration. Risperidone is primarily converted by the cytochrome P450 2D6 (CYP2D6) and 3A4 (CYP3A4) enzymes to 9-hydroxyrisperidone, its active metabolite with equivalent potency to the parent compound. Objective: This study aimed to compare the pharmacokinetics and determine bioequivalence of two risperidone immediate release oral tablets, a test formulation (Risperidone GPO (R) or "Test") and a reference formulation (Risperdal (R) or "Reference"). Method: A single-dose, randomized, fasting, 2-period, 2-sequence, crossover study design with a 2-week washout period was conducted in 23 healthy Thai male volunteers. Blood samples were collected pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 24, 36, 48, 72 and 96 h following an oral administration of 2 mg risperidone. The plasma concentrations of risperidone and 9-hydroxyrisperidone were determined by using a validated HPLC method. Pharmacokinetic parameters of Test and Reference were obtained by noncompartmental analysis. Results: The 90% confidence intervals for Test/Reference ratios of the pharmacokinetic parameters (C-max, AUC(0-1) and AUC(0-infinity)) of both risperidone and its active metabolite (9-hydroxyrisperidone) fell within the acceptable bioequivalence range (80 - 125%) according to ASEAN guideline. Conclusion: The two risperidone formulations are bioequivalent. The test formulation may be used for generic substitution where applicable.