Abstract
The oral absorption of FK506 in solid dispersion formulation was studied in rats. The obtained area under the concentration versus time curve (AUC) increased in a nonlinear fashion with a small dose-dependent increase in the peak blood concentrations (C max). The peak concentration time (T max) was observed within 30 min after administration in all dosing groups (1–10 mg/kg) with or without feeding, whereas the oral absorption of FK506 was reduced to about 50% by gavage at a dose of 1 mg/kg. Participation of first-pass elimination was suggested by comparing the blood levels after infusion via the portal vein with those after infusion via the femoral vein. Further, in an in vitro stability study and an in situ loop absorption study, FK506 was fairly stable in the gastrointestinal juice and was absorbed predominantly from the upper part of the small intestine.
Similar content being viewed by others
REFERENCES
T. Kino, H. Hatanaka, M. Hashimoto, M. Nishiyama, T. Goto, M. Okuhara, M. Kohsaka, H. Aoki, and H. Imanaka. FK506, a novel immunosuppressant isolated from Streptomyces. I. Fermentation, isolation and physico-chemical and biological characteristics. J. Antibiot. 40:1249–1255 (1987).
T. Kino, H. Hatanaka, S. Miyata, N. Inamura, M. Nishiyama, T. Yajima, T. Goto, M. Okuhara, M. Kohsaka, H. Aoki, and T. Ochiai. FK506, a novel immunosuppressant isolated from a Streptomyces. II. Immunosuppressive effect of FK506 in vitro. J. Antibiot. 40:1256–1265 (1987).
T. Honbo, M. Kobayashi, K. Hane, T. Hata, and Y. Ueda. The oral dosage form of FK506. Transplant. Proc. 19(Suppl. 6):17–22 (1987).
R. Venkataramanan, V. S. Warty, M. A. Zemaitis, A. T. Sanghvi, G. J. Burckart, H. Seltman, S. Todo, L. Makowka, and T. E. Starzl. Biopharmaceutical aspects of FK506. Transplant. Proc. 19(Suppl. 6):30–35 (1987).
K. Iwasaki, T. Shiraga, K. Nagase, K. Hirano, K. Nozaki, and K. Noda. Pharmacokinetic study of FK506 in the rat. Transplant. Proc. 23:2757–2759 (1991).
K. Takada, H. Usuda, M. Oh-hashi, H. Yoshikawa, S. Muranishi, and H. Tanaka. Pharmacokinetics of FK506, a novel immunosuppressant, after intravenous and oral administrations to rats. J. Pharmacobio-Dyn. 14:34–42 (1991).
R. Venkataramanan, A. Jain, E. Cadoff, V. Warty, K. Iwasaki, K. Nagase, A. Krajack, O. Imventarza, S. Todo, J. J. Fung, and T. E. Starzl. Pharmacokinetics of FK506: Preclinical and clinical studies. Transplant. Proc. 22(Suppl. 1):52–56 (1990).
Japanese FK506 Study Group. Japanese study of FK506 on kidney transplantation: The benefit of monitoring the whole blood FK506 concentration. Transplant. Proc. 23:3085–3088 (1991).
K. Tamura, M. Kobayashi, K. Hashimoto, K. Kojima, K. Nagase, K. Iwasaki, T. Kaizu, H. Tanaka, and M. Niwa. A highly sensitive method to assay FK506 levels in plasma. Transplant. Proc. 19(Suppl. 6):23–29 (1987).
B. D. Tarr and S. H. Yalkowsky. Enhanced intestinal absorption of cyclosporine in rats through the reduction of emulsion droplet size. Pharm. Res. 6:40–43 (1989).
J. Drewe, C. Beglinger, and T. Kissel. The absorption site of cyclosporin in the human gastrointestinal tract. Br. J. Clin. Pharmacol. 33:39–43 (1992).
R. J. Ptachinski, R. Venkatamaranan, and G. J. Burckart. Clinical Pharmacokinetics of cyclosporin. Clin. Pharmacokin. 11:107–132 (1986).
S. K. Gupta and L. Z. Benet. Food increases the bioavailability of cyclosporine in healthy volunteers. Clin. Pharmacol. Ther. 45:148 (1989).
P. A. Winstanley and M. L'E. Orme. The effects of food on drug bioavailability. Br. J. Clin. Pharmacol. 28:621–628 (1989).
R. J. Sokal, K. E. Johnson, F. M. Karrer, M. R. Narkewicz, D. Smith, and I. Kam. Improvement of cyclosporin absorption in children after liver transplantation by means of water-soluble vitamin E. Lancet 338:212–215 (1991).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kagayama, A., Tanimoto, S., Fujisaki, J. et al. Oral Absorption of FK506 in Rats. Pharm Res 10, 1446–1450 (1993). https://doi.org/10.1023/A:1018967107612
Issue Date:
DOI: https://doi.org/10.1023/A:1018967107612