Pharmaceutical Research

, Volume 19, Issue 9, pp 1362–1367 | Cite as

Evaluation of Pharmacokinetic Interaction Between Cyclosporin A and Probucol in Rats

  • Mari Jiko
  • Ikuko Yano
  • Hiroko Wakasugi
  • Hideyuki Saito
  • Ken-ichi Inui


Purpose. The purpose of this study was to clarify the mechanism of pharmacokinetic interaction between cyclosporin A and probucol in clinical cases.

Methods. The whole blood concentration of cyclosporin A was measured after oral administration of cyclosporin A with or without probucol in rats. Cyclosporin A was administered as three types of solutions: the contents of the conventional formulation (Sandimmun® capsule) diluted with corn oil and the contents of the new microemulsion preconcentrate formulation (Neoral® capsule) diluted with saline or corn oil. The solubility of cyclosporin A and another lipophilic agent tacrolimus in water with or without probucol was also measured.

Results. The area under the blood concentration-time curve (AUC) after the administration of Sandimmun® (corn oil) and Neoral® (corn oil) was significantly decreased to 26% and 41% of the control by coadministration of probucol. However in the case of Neoral® (saline), it was unchanged. The terminal elimination rate constant was not affected by probucol in any type of cyclosporin A solution. The solubility of cyclosporin A or tacrolimus in water dropped to 49% or 16% of the respective control in the presence of probucol.

Conclusion. The interaction between cyclosporin A and probucol is caused by the decreased absorption of cyclosporin A partly based on the lowered solubility in the presence of probucol.

cyclosporin A probucol drug interaction pharmacokinetics 


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Copyright information

© Plenum Publishing Corporation 2002

Authors and Affiliations

  • Mari Jiko
    • 1
  • Ikuko Yano
    • 1
  • Hiroko Wakasugi
    • 1
  • Hideyuki Saito
    • 1
  • Ken-ichi Inui
    • 1
  1. 1.Department of Pharmacy, Kyoto University Hospital, Faculty of MedicineKyoto UniversitySakyo-ku, KyotoJapan

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