Archives of Pharmacal Research

  • 제25권3호
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  • Pages.387-391
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  • 2002
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  • 0253-6269(pISSN)
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  • 1976-3786(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

Interspecies Comparison of the Oral Absorption of Itraconazole in Laboratory Animals

  • 발행 : 2002.06.01
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초록

The oral absorption and disposition of itraconazole were studied in rats, rabbits and dogs. Serum levels of itraconazole and its active metabolite, hydroxyitraconazole, were determined by a validated HPLC method. The absorption of itraconazole was relatively rapid in rats and dogs but was slower in rabbits. The terminal elimination half-life ($T_{1/2,{\lambda}z}$), time to the peak concentration ($T_{max}$), dose and weight normalized area under the curve (AUC) and the peak concentration ($C_{max}$) of itraconazole found in the dog were comparable to those reported in humans. As in humans, the metabolite to parent drug AUC ratios in rats and dogs were greater than unity but was less in rabbits. The dog appears to be an appropriate animal model while the rat, not the rabbit, may be used as an alternative animal model in predicting the oral absorption of itraconazole in humans.

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참고문헌

  1. Aoyagi, N., Ogata, H., Kaniwa, N., Uchiyama, M., Yasuda, Y and Tanioka, Y., Gastric emptying of tablets and granules in humans, dogs, pigs, and stomach-emptying-controlled rabbits. J. Pharm. Sci., 81,1170-1174 (1992) https://doi.org/10.1002/jps.2600811208
  2. Barone, J.A, Koh, J.G., Bierman, R.H., Colaizzi, J.L., Swanson, K.A., Gaffar, M.C., Moskovitz, B.L., Mechlinski, W. and Van de Velde, V., Food interaction and steady-state pharmacokinetics of itraconazole capsules in healthy male volunteers. Antmicrob. Agents Chemother., 37, 778-784 (1993) https://doi.org/10.1128/AAC.37.4.778
  3. Chiou W.L., Riegelman, S. and Amberg, J.R, Complications in using rabbits for the study of oral drug absorption. Chem. Pharm. Bull., 17,2170-2173 (1969) https://doi.org/10.1248/cpb.17.2170
  4. Davies, B. and Morris, T., Physiological parameters in laboratory animals and humans. Pharm. Res., 10, 1093-1095(1993)
  5. Dressman, J. and Yamada, K., Animal models for oral drug absorption. In Welling, P.G., Tse, F.L.S., Dighe, S.V. (Eds.). Pharmaceuticel Bioequivalence. Marcel Dekker Inc., New York pp.235-266, 1991
  6. Dupont, B. and Drouhet, E., Early experience with itraconazole in vitro and in patients: pharmacokinetic studies and clinical results, Rev. Infect. Dis., 9, S71-S76 (1987)
  7. Grant S.M. and Clissold, S.P., Itraconazole. A review of its pharmacodynamic and pharmacokinetic properties and the apeutic use in superficial and systemic mycoses. Drugs, 37, 310-344(1989) https://doi.org/10.2165/00003495-198937030-00003
  8. Hardin, T.C., Graybill, J.R., Fetchick, R., Woestenborghs, R., Rinaldi, M.G. and Kuhn, J.G., Pharmacokinetics of itraconazole following oral administration to normal volunteers. Antimicrob. Agents Chemother., 32, 1310-1313 (1988) https://doi.org/10.1128/AAC.32.9.1310
  9. Haria, M., Bryson, H.M. and Goa, K.L., Itraconazole: a reaopraisal of its pharmacological properties and therapeutic use in the management of superficial fungal infections. Drugs, 51, 585-620 (1996) https://doi.org/10.2165/00003495-199651040-00006
  10. Heykants, J., Michiels, M., Meuldermans, W., Monbaliu, J., Lavrijsen, K., Van Peer, A., Levron, J.C., Woestenborghs, R. and Cauwenbergh, G., The pharmacokinetics of itraconazole in animals and man: an overview. In Fromtling, R.A, (Ed.). Recent Trends in the Discovery, Development and Evaluation of Antifungal Agents. J. R Prous Science Publishers, Barcelona, pp. 223-249,1987
  11. Heykants, J., Van Peer, A., Van de Velde, V., Van Rooy, P., Meuldermans, W., Lavrijsen, K., Woestenborghs, .R, Van Cutsem, J. and Cauwenbergh, G., The clinical pharmacokinetics of itraconazole: an overview. Mycoses, 32, 67-87 (1989) https://doi.org/10.1111/j.1439-0507.1989.tb02296.x
  12. Heykants, J., Van Peer, A., Lavrijsen, K., Meuldermans, W., Woestenborghs, R. and Cauwenbergh, G., Pharmacokinetics of oral antifungals and their clinical implications. Br. J. Clin. Pract. Suppl., 71,50-56 (1990)
  13. Lange, D., Pavao, J.H., Wu, J. and Klausner, M., Effect of a cola beverage on the bioavailability of itraconazole in the presence of $H_{2}$ blockers. J. Clin. Pharmacol., 37, 535-540 (1997) https://doi.org/10.1002/j.1552-4604.1997.tb04332.x
  14. Van Peer, A., Woestenborghs, R., Heykants, J., Gasparini, R. and Cauwenbergh, G., The effects of food and dose on the oral systemic availability of itraconazole in healthy subjects. Eur. J. Clin. Pharmacol., 36, 423-426 (1989) https://doi.org/10.1007/BF00558308
  15. Yoo, S.D., Kang, E., Jun, H., Shin, B.S., Lee, K.C. and Lee, K.H., Absorption, first-pass metabolism, and disposition of itraconazole in rats. Chem. Pharm. Bull., 48,798-801 (2000) https://doi.org/10.1248/cpb.48.798
  16. Zimmermann, T., Yeates, R.A., Albrecht, M., Laufen, H. and Wildfeuer, A., Influence of concomitant food intake on the gastrointestinal absorption of fluconazole and itraconazole in Japanese subjects. Int. J. Clin. Pharmacol. Res., 14, 87-93(1994)