Pharmacokinetic study of the structural components of adenosine diphosphate-encapsulated liposomes coated with fibrinogen g-chain dodecapeptide as a synthetic platelet substitutes

Kazuaki Taguchi, Hayato Ujihira, Shigeru Ogaki, Hiroshi Watanabe, Atsushi Fujiyama, Mami Doi, Yosuke Okamura, Shinji Takeoka, Yasuo Ikeda, Makoto Handa, Masaki Otagiri, Toru Maruyama

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    Fibrinogen g-chain (dodecapeptide HHLGGAKQAGDV, H12)-coated, ADP-encapsulated liposomes [H12-(ADP)-liposomes] were developed as a synthetic platelet alternative that specifically accumulates at bleeding sites as the result of interactions with activated platelets via glycoprotein IIb/IIIa and augments platelet aggregation by releasing ADP. The aim of this study is to characterize the pharmacokinetic properties of H12-(ADP)-liposomes and structural components in rats, and to predict the blood retention of H12-(ADP)-liposomes in humans. With use of H12-(ADP)-liposomes in which the encapsulated ADP and liposomal membrane cholesterol were radiolabeled with 14C and 3H, respectively, it was found that the time courses for the plasma concentration curves of 14C and 3H radioactivity showed that the H12-(ADP)-liposomes remained intact in the blood circulation for up to 24 hours after injection, and were mainly distributed to the liver and spleen. However, the 14C and 3H radioactivity of H12-(ADP)-liposomes disappeared from organs within 7 days after injection. The encapsulated ADP was metabolized to allantoin, which is the final metabolite of ADP in rodents, and was mainly eliminated in the urine, whereas the cholesterol was mainly eliminated in feces. In addition, the half-life of the H12-(ADP)-liposomes in humans was predicted to be approximately 96 hours from pharmacokinetic data obtained for mice, rats, and rabbits using an allometric equation. These results suggest that the H12-(ADP)-liposome has potential with proper pharmacokinetic and acceptable biodegradable properties as a synthetic platelet substitute.

    Original languageEnglish
    Pages (from-to)1584-1591
    Number of pages8
    JournalDrug Metabolism and Disposition
    Volume41
    Issue number8
    DOIs
    Publication statusPublished - 2013 Aug

    Fingerprint

    Liposomes
    Adenosine Diphosphate
    Fibrinogen
    Blood Platelets
    Pharmacokinetics
    Radioactivity
    Cholesterol
    Allantoin
    Platelet Membrane Glycoproteins
    Platelet Glycoprotein GPIIb-IIIa Complex
    Injections
    Blood Circulation
    Platelet Aggregation
    Feces
    Half-Life
    Rodentia
    Spleen
    Urine
    Hemorrhage
    Rabbits

    ASJC Scopus subject areas

    • Pharmacology
    • Pharmaceutical Science

    Cite this

    Pharmacokinetic study of the structural components of adenosine diphosphate-encapsulated liposomes coated with fibrinogen g-chain dodecapeptide as a synthetic platelet substitutes. / Taguchi, Kazuaki; Ujihira, Hayato; Ogaki, Shigeru; Watanabe, Hiroshi; Fujiyama, Atsushi; Doi, Mami; Okamura, Yosuke; Takeoka, Shinji; Ikeda, Yasuo; Handa, Makoto; Otagiri, Masaki; Maruyama, Toru.

    In: Drug Metabolism and Disposition, Vol. 41, No. 8, 08.2013, p. 1584-1591.

    Research output: Contribution to journalArticle

    Taguchi, Kazuaki ; Ujihira, Hayato ; Ogaki, Shigeru ; Watanabe, Hiroshi ; Fujiyama, Atsushi ; Doi, Mami ; Okamura, Yosuke ; Takeoka, Shinji ; Ikeda, Yasuo ; Handa, Makoto ; Otagiri, Masaki ; Maruyama, Toru. / Pharmacokinetic study of the structural components of adenosine diphosphate-encapsulated liposomes coated with fibrinogen g-chain dodecapeptide as a synthetic platelet substitutes. In: Drug Metabolism and Disposition. 2013 ; Vol. 41, No. 8. pp. 1584-1591.
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    AU - Ogaki, Shigeru

    AU - Watanabe, Hiroshi

    AU - Fujiyama, Atsushi

    AU - Doi, Mami

    AU - Okamura, Yosuke

    AU - Takeoka, Shinji

    AU - Ikeda, Yasuo

    AU - Handa, Makoto

    AU - Otagiri, Masaki

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