BACKGROUND AND OBJECTIVES: Beraprost sodium (BPS), an orally administrable prostaglandin I2 derivative, is used for the treatment of chronic arterial occlusion and pulmonary arterial hypertension and has potential efficacy in nephropathy. Beraprost sustained release (beraprost SR) is an oral sustained-release formulation of BPS. To confirm the dose rationale reported in a multi-regional study of nephropathy patients in Asia, this open-label study evaluated ethnic differences in the pharmacokinetic profiles of BPS and its active diastereomer (BPS-314d) after beraprost SR administration among healthy Japanese, Chinese, and Korean adult males. METHODS: Twelve healthy subjects in each ethnic group were enrolled. Subjects received a single oral dose of 120 μg beraprost SR under fasting conditions. RESULTS: The geometric mean ratio (90% confidence interval) of the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUClast) of BPS was 1.12 (0.85-1.48) and 1.40 (1.05-1.86) in Chinese, and 1.18 (0.90-1.55) and 1.18 (0.89-1.58) in Korean compared to Japanese subjects. These differences were not clinically relevant. Similarly, differences in the Cmax and AUClast of BPS-314d were also small among the ethnic groups. Urinary excretion of BPS and BPS-314d was limited in all ethnic groups. Together, these findings indicate that the pharmacokinetics of beraprost SR are not affected by ethnic background. CONCLUSIONS: There were no clinically meaningful ethnic differences in the pharmacokinetics of BPS and BPS-314d following beraprost SR administration among Japanese, Chinese and Korean populations.
BACKGROUND AND OBJECTIVES:Beraprost sodium (BPS), an orally administrable prostaglandin I2 derivative, is used for the treatment of chronic arterial occlusion and pulmonary arterial hypertension and has potential efficacy in nephropathy. Beraprost sustained release (beraprost SR) is an oral sustained-release formulation of BPS. To confirm the dose rationale reported in a multi-regional study of nephropathypatients in Asia, this open-label study evaluated ethnic differences in the pharmacokinetic profiles of BPS and its active diastereomer (BPS-314d) after beraprost SR administration among healthy Japanese, Chinese, and Korean adult males. METHODS: Twelve healthy subjects in each ethnic group were enrolled. Subjects received a single oral dose of 120 μg beraprost SR under fasting conditions. RESULTS: The geometric mean ratio (90% confidence interval) of the maximum plasma concentration (Cmax) and area under the plasma concentration-time curve from time 0 to time of the last quantifiable concentration (AUClast) of BPS was 1.12 (0.85-1.48) and 1.40 (1.05-1.86) in Chinese, and 1.18 (0.90-1.55) and 1.18 (0.89-1.58) in Korean compared to Japanese subjects. These differences were not clinically relevant. Similarly, differences in the Cmax and AUClast of BPS-314d were also small among the ethnic groups. Urinary excretion of BPS and BPS-314d was limited in all ethnic groups. Together, these findings indicate that the pharmacokinetics of beraprost SR are not affected by ethnic background. CONCLUSIONS: There were no clinically meaningful ethnic differences in the pharmacokinetics of BPS and BPS-314d following beraprost SR administration among Japanese, Chinese and Korean populations.
Authors: Y Itoh; A Nakai; H Kakizawa; M Makino; K Fujiwara; T Kobayashi; T Kato; M Nagata; N Oda; H Katsumata; A Nagasaka; M Itoh Journal: Horm Res Date: 2001