Single- and Multiple-Dose Pharmacokinetics and Tolerability of Limaprost in Healthy Chinese Subjects

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• 作者：Hong Chen ; Qi Zhang ; Xiaojiao Li ; Hong Zhang ; Yanfu Sun…
• 刊名：Clinical Drug Investigation
• 出版年：2015
• 出版时间：March 2015
• 年：2015
• 卷：35
• 期：3
• 页码：151-157
• 全文大小：354 KB
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• 刊物主题：Pharmacotherapy; Pharmacology/Toxicology; Internal Medicine;
• 出版者：Springer International Publishing
• ISSN：1179-1918

文摘

Background and Objectives Limaprost, a prostaglandin E1 analogue, is used to treat various symptoms in patients with ischemic diseases. The present study was designed to determine the pharmacokinetics and tolerability of single and multiple oral doses of limaprost 5?μg tablets in healthy Chinese subjects. Methods Single and multiple doses of 5-μg limaprost were orally administered to 12 healthy Chinese subjects. There was a 2-week washout period between single and multiple dosing. Blood samples were collected at various times. Indomethacin and aspirin were added to the blood samples to inhibit the endogenous release of prostaglandins during the sample processing. Plasma limaprost was measured by a two-dimensional liquid chromatography-tandem mass spectrometry method. Results After single dosing, limaprost was rapidly absorbed (time to reach maximum plasma concentration [t max]?=?22.50?min) and eliminated (elimination half-life [t ?]?=?21.70?min), with the maximum plasma concentration (C max) being 2.56?pg/mL and area under the concentration-time curve (AUC) from time 0 to the last quantifiable time point (AUC0–t) being 70.68?pg·min/mL. There were significant inter-individual variations in the AUCs for both single- and multiple-dose regimens. The values of C max, AUC, t ? and t max were not statistically different between single and multiple dosing. The accumulation factor R was 0.609?±?0.432 (R? Conclusions Limaprost is rapidly absorbed after oral administration and is rapidly eliminated, with no accumulation after multiple dosing. The drug is well tolerated and no serious adverse events occurred.