Bioequivalence of Samchundang Berastolin tablet to Jeil Berasil tablet (beraprost sodium 20 μg)

摘要

Beraprost sodium, sodium (±)-(1R*,2R*,3aS*,8bS*)-2,3,3a,8b-tetrahydro-2-hydroxy-1-[(E)-(3S*)-3-hydroxy-4-methyl-1-octen-6-ynyl]-1H-cyclopenta[b]benzofuran-5-butyrate), an orally absorbable prostacyclin derivative (PGI2), has marked ischemic symptom treatments like ulcer and pain with chronic arterial occlusion. The purpose of the present study was to evaluate the bioequivalence of two beraprost sodium tablets, Samchundang Berastolin tablet (Samchundang Pharm. Co., Ltd.) and Jeil Berasil tablet (Jeil Pharm. Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The in vitro release of beraprost from the two beraprost sodium formulations was tested using KP IX Apparatus II method with various dissolution media. Thirty-two healthy Korean male volunteers, 23.44 ± 1.48 years in age and 65.95 ± 8.94 kg in body weight, were divided into two groups and a randomized 2 × 2 crossover study was employed. After single administration, three tablets containing 20 μg as beraprost sodium, blood samples were taken at predetermined time intervals and the concentrations of beraprost in serum were determined using a LC/MS/MS method with multiple reaction-monitoring. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as AUCt, Cmax and Tmax were calculated, and computer programs (Equiv Test and K-BE Test 2002) were utilized for the statistical analysis of the parameters using logarithmically transformed AUCt, Cmax and un-transformed Tmax. The results showed that the differences between two formulations based on the reference drug, Jeil Berasil tablet, were 2.12, 0.15 and 4 % for AUCt, Cmax, and Tmax, respectively. There were no sequence effects between two formulations in these parameters. The 90 % confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8-log 1.25 (e.g., log 0.9114-log 1.0912 and log 0.8471-log 1.1253 for AUCt and Cmax, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Samchundang Berastolin tablet was bioequivalent to Jeil Berasil tablet.