Pharmacokinetics of 9α-fluoromedroxyprogesterone acetate in rats: comparison with medroxyprogesterone acetate
1999; Wiley; Volume: 20; Issue: 6 Linguagem: Inglês
10.1002/(sici)1099-081x(199909)20
ISSN1099-081X
AutoresDaisuke Kozutsumi, Akihiro Kawashima, Takako Sugimoto, Yumi Kotohda, Shiho FUJIMORI, Masao Takami, Tetsuya Kohno, Tsutomu Oikawa, Eiichi Sugino, Tominari Choshi, Satoshi Hibino,
Tópico(s)DNA and Nucleic Acid Chemistry
ResumoBiopharmaceutics & Drug DispositionVolume 20, Issue 6 p. 277-284 Original Paper Pharmacokinetics of 9α-fluoromedroxyprogesterone acetate in rats: comparison with medroxyprogesterone acetate Daisuke Kozutsumi, Corresponding Author Daisuke Kozutsumi Laboratory of Pharmacokinetics and Drug Metabolism, Department of Pharmaceutical Development, Meiji Institute of Health Science, Meiji Milk Products Company, Limited, Odawara, Kanagawa, JapanLaboratory of Pharmacokinetics and Drug Metabolism, Department of Pharmaceutical Development, Meiji Institute of Health Science, Meiji Milk Products Company, Limited, 540 Naruda, Odawara, Kanagawa 250-0862, JapanSearch for more papers by this authorAkihiro Kawashima, Akihiro Kawashima Laboratory of Pharmacokinetics and Drug Metabolism, Department of Pharmaceutical Development, Meiji Institute of Health Science, Meiji Milk Products Company, Limited, Odawara, Kanagawa, JapanSearch for more papers by this authorTakako Sugimoto, Takako Sugimoto Laboratory of Pharmacokinetics and Drug Metabolism, Department of Pharmaceutical Development, Meiji Institute of Health Science, Meiji Milk Products Company, Limited, Odawara, Kanagawa, JapanSearch for more papers by this authorYumi Kotohda, Yumi Kotohda Laboratory of Pharmacokinetics and Drug Metabolism, Department of Pharmaceutical Development, Meiji Institute of Health Science, Meiji Milk Products Company, Limited, Odawara, Kanagawa, JapanSearch for more papers by this authorShiho Fujimori, Shiho Fujimori Laboratory of Pharmacokinetics and Drug Metabolism, Department of Pharmaceutical Development, Meiji Institute of Health Science, Meiji Milk Products Company, Limited, Odawara, Kanagawa, JapanSearch for more papers by this authorMasao Takami, Masao Takami Laboratory of Pharmacokinetics and Drug Metabolism, Department of Pharmaceutical Development, Meiji Institute of Health Science, Meiji Milk Products Company, Limited, Odawara, Kanagawa, JapanSearch for more papers by this authorTetsuya Kohno, Tetsuya Kohno Laboratory of Pharmacokinetics and Drug Metabolism, Department of Pharmaceutical Development, Meiji Institute of Health Science, Meiji Milk Products Company, Limited, Odawara, Kanagawa, JapanSearch for more papers by this authorTsutomu Oikawa, Tsutomu Oikawa Department of Cancer Therapeutics, The Tokyo Metropolitan Institute of Medical Science (Rinshoken), Bunkyo-ku, Tokyo, JapanSearch for more papers by this authorEiichi Sugino, Eiichi Sugino Faculty of Pharmacy and Pharmaceutical Science, Fukuyama University, Fukuyama, Hiroshima, JapanSearch for more papers by this authorTominari Choshi, Tominari Choshi Faculty of Pharmacy and Pharmaceutical Science, Fukuyama University, Fukuyama, Hiroshima, JapanSearch for more papers by this authorSatoshi Hibino, Satoshi Hibino Faculty of Pharmacy and Pharmaceutical Science, Fukuyama University, Fukuyama, Hiroshima, JapanSearch for more papers by this author Daisuke Kozutsumi, Corresponding Author Daisuke Kozutsumi Laboratory of Pharmacokinetics and Drug Metabolism, Department of Pharmaceutical Development, Meiji Institute of Health Science, Meiji Milk Products Company, Limited, Odawara, Kanagawa, JapanLaboratory of Pharmacokinetics and Drug Metabolism, Department of Pharmaceutical Development, Meiji Institute of Health Science, Meiji Milk Products Company, Limited, 540 Naruda, Odawara, Kanagawa 250-0862, JapanSearch for more papers by this authorAkihiro Kawashima, Akihiro Kawashima Laboratory of Pharmacokinetics and Drug Metabolism, Department of Pharmaceutical Development, Meiji Institute of Health Science, Meiji Milk Products Company, Limited, Odawara, Kanagawa, JapanSearch for more papers by this authorTakako Sugimoto, Takako Sugimoto Laboratory of Pharmacokinetics and Drug Metabolism, Department of Pharmaceutical Development, Meiji Institute of Health Science, Meiji Milk Products Company, Limited, Odawara, Kanagawa, JapanSearch for more papers by this authorYumi Kotohda, Yumi Kotohda Laboratory of Pharmacokinetics and Drug Metabolism, Department of Pharmaceutical Development, Meiji Institute of Health Science, Meiji Milk Products Company, Limited, Odawara, Kanagawa, JapanSearch for more papers by this authorShiho Fujimori, Shiho Fujimori Laboratory of Pharmacokinetics and Drug Metabolism, Department of Pharmaceutical Development, Meiji Institute of Health Science, Meiji Milk Products Company, Limited, Odawara, Kanagawa, JapanSearch for more papers by this authorMasao Takami, Masao Takami Laboratory of Pharmacokinetics and Drug Metabolism, Department of Pharmaceutical Development, Meiji Institute of Health Science, Meiji Milk Products Company, Limited, Odawara, Kanagawa, JapanSearch for more papers by this authorTetsuya Kohno, Tetsuya Kohno Laboratory of Pharmacokinetics and Drug Metabolism, Department of Pharmaceutical Development, Meiji Institute of Health Science, Meiji Milk Products Company, Limited, Odawara, Kanagawa, JapanSearch for more papers by this authorTsutomu Oikawa, Tsutomu Oikawa Department of Cancer Therapeutics, The Tokyo Metropolitan Institute of Medical Science (Rinshoken), Bunkyo-ku, Tokyo, JapanSearch for more papers by this authorEiichi Sugino, Eiichi Sugino Faculty of Pharmacy and Pharmaceutical Science, Fukuyama University, Fukuyama, Hiroshima, JapanSearch for more papers by this authorTominari Choshi, Tominari Choshi Faculty of Pharmacy and Pharmaceutical Science, Fukuyama University, Fukuyama, Hiroshima, JapanSearch for more papers by this authorSatoshi Hibino, Satoshi Hibino Faculty of Pharmacy and Pharmaceutical Science, Fukuyama University, Fukuyama, Hiroshima, JapanSearch for more papers by this author First published: 20 January 2000 https://doi.org/10.1002/(SICI)1099-081X(199909)20:6 3.0.CO;2-TCitations: 4AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Medroxyprogesterone acetate (MPA) is widely used in endocrine therapy for breast cancer and other diseases. Recently, it has been demonstrated that 9α-fluoromedroxyprogesterone acetate (FMPA) also has anti-tumour activity in chemical-induced rat mammary tumour and its activity is greater than that of MPA. In the present study, the physico-chemical properties of FMPA and MPA and their pharmacokinetics in female rats were investigated. Partition coefficients (log P) of FMPA and MPA were 3.1 and 3.8, respectively, while the solubilities of FMPA and MPA in phosphate buffer saline were 3.8 and 1.1 μg/mL, respectively. When the two agents were intravenously or orally administered into female rats, there was no significant difference between their plasma concentrations. However, unmetabolized drug excreted into urine accounted for 4.7 and 0.7% of the intravenous dose of FMPA and MPA, respectively. The free fraction of FMPA in rat plasma was approximately four times that of MPA. Assuming the well-stirred model, hepatic intrinsic clearances of FMPA and MPA were estimated to be 64 and 293 L/h per kg, respectively. In addition, the free fraction of FMPA in blood is estimated to be higher than that of MPA, which may explain the higher anti-tumour activity. Copyright © 1999 John Wiley & Sons, Ltd. Citing Literature Volume20, Issue6September 1999Pages 277-284 RelatedInformation
Referência(s)