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

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Abstract

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 ½] = 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 ½ and t max were not statistically different between single and multiple dosing. The accumulation factor R was 0.609 ± 0.432 (R < 1), indicating that there was no accumulation after multiple dosing. There were no statistically significant differences in pharmacokinetic parameters for both single and multiple dosing between female and male subjects. The drug was well tolerated, with no severe adverse events being observed.

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.

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Acknowledgments

This work was financially supported by National Major Scientific and Technological Special Project for “Significant New Drugs Development” during the Twelfth Five-year Plan Period of China (Project: 2014ZX09303303) and the National Natural Science Foundation of China (Project: 81430087).

Conflict of interest

The authors have indicated that they have no other conflicts of interest regarding the content of this article.

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Author notes

    Authors and Affiliations

    1. Phase I Clinical Trial Unit, The First Hospital of Jilin University, China-Frontage USA, Jilin University, Xinmin Street, Changchun, Jilin, 130021, China

      Hong Chen, Qi Zhang, Xiaojiao Li, Hong Zhang, Yanfu Sun, Chengjiao Liu & Yanhua Ding

    2. Clinical Pharmacology Center, Research Institute of Translational Medicine, First Hospital of Jilin University, Jilin University, Changchun, Jilin, China

      Lei Yin

    3. Department of Clinical Medicine, Bethune Medical School Jilin University, Changchun, Jilin, China

      Yuchen Cao

    4. College of Life Science, Jilin University, Changchun, Jilin, China

      Jingkai Gu

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    1. Hong Chen
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    Correspondence to Yanhua Ding.

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    H. Chen and Q. Zhang contributed equally to this work.

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    Chen, H., Zhang, Q., Li, X. et al. Single- and Multiple-Dose Pharmacokinetics and Tolerability of Limaprost in Healthy Chinese Subjects. Clin Drug Investig 35, 151–157 (2015). https://doi.org/10.1007/s40261-014-0265-3

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    • DOI: https://doi.org/10.1007/s40261-014-0265-3

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