Pharmacokinetic and bioavailability studies using 5 mg mosapride tablets in healthy Korean volunteers

摘要

Aim: Mosapride is a gastroprokinetic agent, a 5-HT4 receptor agonist and 5-HT3 receptor antagonist exhibiting no activity at dopamine D2, 5-HT1 and 5-HT2 receptors. This study was performed to compare basic pharmacokinetic (PK) characteristics of mosapride for Korean young adults and to evaluate the bioequivalence (BE) of two formulations of drugs mosapride. Volunteers and methods: For pharmacokinetic and bioavailability of 5 mg mosapride tablets in healthy Korean adults, a randomized, twoway, crossover bioequivalence study in 23 healthy Korean volunteers (M : F = 16 : 7) was conducted to compare bioavailability of two formulation of 5 mg mosapride citrate tablets, Moprid? (Chung Kun Dang Pharm Co., Ltd., Korea) as a test and Gasmotin? (Daewoong Pharm Co., Ltd., Korea) as a reference drug. Subjects were administered single dosage of 3 tablets of each formulation with 240 ml water after 10 h overnight fasting on 2 treatment days separated by 1-week washout period. Before and after dosing, blood sample were collected at 0, 0.25, 0.5, 0.8, 1.0, 1.5, 2, 2.5, 3, 4, 6, 8, 12 and 24 h and analyzed by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the range 1.28-192 ng/ml with the lowest limit of quantification of 1.28 ng/ml. Results: Several PK characteristics were determined from the plasma samples, and data from reference and test fomulations in the plasma were represented such as AUC0-t (184.4 vs. 179.6 ngxh/ml), AUC0-∞ (192.8 vs. 186.6 ngxh/ml), Cmax (98.9 vs. 84.4 ng/ml), tmax (0.8 vs. 0.7 h), half-life (2.4 vs. 2.3 h), Ke (0.289 vs. 0.301), respectively. AUC0-t and Cmax were tested for bioequivalence after log-transformation of plasma data. PK characteristics with 90% confidence interval (CI) of test/reference ratio based on ANOVA analysis were 0.842-1.163 for AUC0-t and 0.753-1.088 for Cmax. PK characteristics with 90% CI were within the bioequivalence range of 80-125% of FDA statistical limit. Cmax with 90% CI were not within the bioequivalence range of 80-125% of FDA statistical limit. However, this result was assessed to bioequivalence in accordance with the "Bioequivalence Test Guidelines" outlined in No. 2005-31 of the KFDA. Conclusion: Therefore, both mosapride formulations were bioequivalent during fasting state in healthy Korean adults.