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| the progestin st 1435-rapid metabolism in man |
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2楼2009-07-24 11:56:35
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这篇文章我查了一下，只能给作者和摘要。 The progestin ST 1435—rapid metabolism in man This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. Oskari Heikinheimo a, , Gabriela Noe b, Maija Haukkamaa a and Pekka Lähteenmäki a a Steroid Research Laboratory, Department of Medical Chemistry, University of Helsinki, Helsinki, Finland b Consultorio de Planificacón Familiar, Instituto Chileno de Medicina Reproductiva, Santiago, Chile Received 31 March 1994; accepted 6 June 1994. Available online 13 February 2004. Abstract Parenterally administered ST 1435 (Nestorone™  is highly potent for contraception, and ovulation can be inhibited with very low serum levels of ST 1435. Orally administered ST 1435 is ineffective in various laboratory animals, presumably due to extensive first-pass metabolism. Thus, ST 1435 has been proposed for lactational contraception, to be metabolized by the suckling infant. We have studied the metabolism of ST 1435 in female volunteers following oral (10 mg), intravenous (iv) (0.1 mg) and transdermal (4.5–9.0 mg) routes of ST 1435 administration. Preliminary studies using rats were performed to develop the methodology of high performance-liquid chromatography (HPLC) fractionation and ST 1435-RIA detection. Rat portal serum revealed 4 distinct peaks of immunoreactive material with the retention times (Rt's) of 7.5, 10, 14.5 and 17.5 min (ST 1435 = 10 min). In systemic serum, only the peak with the Rt of 7.5 min could be detected. Therefore, orally administered ST 1435 is very effectively metabolized by the rat liver; this also explains the previously observed lack of biological effects of oral ST 1435. Following oral administration of ST 1435 to two women, the Rt of the major peak was 10 min. The magnitude of the ST 1435 peak decreased rapidly, and at 24h following ingestion, no ST 1435 could be detected by this method. The t of ST 1435 was ˜ 1–2h. In addition, two minor peaks with Rt's of 4.5 and 16 min could be detected with the ST 1435 RIA at 1–4h following oral ingestion. Competitive receptor binding assays using the human uterine progesterone receptors (hPR) revealed that the ST 1435 fraction exhibits strong binding affinity towards the hPR; thus, in the human, a small fraction of biologically active ST 1435 seems to escape from the first-pass metabolism following oral intake. Following iv and transdermal administration of ST 1435, the only detectable peak with ST 1435-RIA was that of ST 1435. Similar magnitude of the ST 1435 peaks following oral administration of 10 mg and iv administration of 0.1 mg indicated that the bioavailability of ST 1435 is low. These data seem to confirm the suspicion that orally administered ST 1435 is also rapidly metabolized in the human, therefore encouraging further evaluation of ST 1435 during lactation. However, the rapid metabolism seen after oral intake can be successfully circumvented by sustained parenteral administration of ST 1435.Author Keywords: Author Keywords: Nestorone; progestin; first-pass metabolism; rat; high performance liquid chromatography; radioimmunoassay [ Last edited by 名人6520 on 2009-7-24 at 15:32 ] |
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5楼2009-07-24 16:01:18
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6楼2009-07-24 16:18:26
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7楼2009-07-25 08:23:24
