Study of phanuacokinetic properties of cyclosporiue a after subcutaneous injection in cynomolgus monkey

Iori Kisu, Yojiro Kato, Hideaki Tsuchiya, Lkuo Kawamoto, Takahiro Nakagawa, Kazumasa Ogasawara, Tomohisa Hayakawa, Yasuko Yamayoshi, OSamu Iketani, Makoto Mihara, Kouji Banno, Shin Ichi Sato, Takashi Shiina, Daisuke Aoki

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1 Citation (Scopus)

Abstract

Intramuscular or intravenous injection of Cyclosporine A (CyA) has been performed in some transplantation animal studies, including non-hwnan primates. However, the pharmacokinetics after subcutaneous (s.c.) injection of CyA in cynomolgus monkey has not been reported. In this study CyA was administered subcutaneously in cynomolgus monkeys at three doses and investigated the pharmacokinetics. Six female cynomolgus monkeys were used in the study. CyA was administered once daily at a prescribed time for 7 days in the back of each monkey at doses of 2.5, 5 or 10 mg kg-1in different administration periods. The blood trough level of CyA was measured on consecutive days. On days 0, 1 and 4, the level was measured 2, 4, 6, 8 and 12 h after CyA administration. The mean trough concentrations on day 4 in the 6 animals at doses of 2.5, 5 and 1 0 mg kg_, were 162±56, 356±97 and 652±137 ng mL, respectively, showiug a dose-dependent increase. The average Tmax range at each concentration on days 0 and 4 was 5-11 hand was 5-6 h on day 4 at steady state, with Cmax tending to be not high. The T112 showed general prolongations that were 14-19 h on day 4. Average pharmacokinetic data on day 4 showed dose-dependent and almost linear increases in AUC= which were 9822±3473, 24323±9520 and 43418±12591 ug.hr mL_,at dose of 2.5, 5 and 10 mg kg-', respectively. The pharmacokinetics of CyA after s.c. injection in cynomolgus monkeys showed a slow absorption phase, a Cmax that is not high and a prolouged elimination phase. The linearity of the AUC with dose and the high AUC and trough level in the early days after first administration suggest high bioavailability and sufficient efficacy after s.c. injection.

Original languageEnglish
Pages (from-to)487-493
Number of pages7
JournalInternational Journal of Pharmacology
Volume10
Issue number8
DOIs
Publication statusPublished - 2014 Jan 1

Keywords

  • Cyclosporine A
  • Cynomolgus monkey
  • Pharmacokinetics
  • Subcutaneous injection
  • Uterus trans lantation

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Kisu, I., Kato, Y., Tsuchiya, H., Kawamoto, L., Nakagawa, T., Ogasawara, K., Hayakawa, T., Yamayoshi, Y., Iketani, OS., Mihara, M., Banno, K., Sato, S. I., Shiina, T., & Aoki, D. (2014). Study of phanuacokinetic properties of cyclosporiue a after subcutaneous injection in cynomolgus monkey. International Journal of Pharmacology, 10(8), 487-493. https://doi.org/10.3923/ijp.2014.487.493