性格和药理效应的R / S-verapamil慢性房颤患者:一项调查比较单一和多个剂量。
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会先D,弗洛姆MF Morike K, Drescher年代,Kuhlkamp V, Eichelbaum M
性格和药理效应的R / S-verapamil慢性房颤患者:一项调查比较单一和多个剂量。
69年5月,中国新药杂志。2001 (5):324 - 32。doi: 10.1067 / mcp.2001.115125。
- PubMed ID
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11372000 (在PubMed]
- 文摘
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背景:外消旋(R / S) -维拉帕米广泛应用于慢性心房纤颤的管理。负变导效应主要是由S对映体,这是优先代谢。以前的研究报告的积累R / S -维拉帕米在长期口服治疗慢性房颤患者。然而,维拉帕米和药理效应的具体配置没有评估。因此不确定性仍需要剂量调整。beplayapp方法:利用稳定同位素技术和立体定向分析,我们比较了静脉注射的药代学和药效学(10毫克的d (7) - R / S维拉帕米)和口头(240毫克缓释(SR) d (0) - R / S维拉帕米)R维拉帕米和S维拉帕米第一剂量(第一天)和后3周后(21天)连续8患者长期口服治疗心房纤颤。两天学习,获得的血清样本的分析(7)- d (0) - r维拉帕米和维拉帕米。心率(HR)监测心电描记法(每个血液样本)和霍尔特心电描记法(在这项研究之前,第一天,21天)。结果:与第一天相比,清除口腔R维拉帕米和S维拉帕米在21天显著降低(1007 + / - 380和651 + / - 253毫升/分钟(-35%)和5481 + / - 2731和2855 + / - 1097毫升/分钟(-48%),分别为;P < . 05),而只有适度降低R观察静脉注射维拉帕米和S维拉帕米(分别为-23%和-14%,不重要)。 Mean HR (89 +/- 11 bpm before verapamil) was effectively reduced, with the same effects on day 1 (68 +/- 8 bpm) and day 21 (68 +/- 8 bpm). Compared with day 1, the HR reduction per ng/mL of S -verapamil (calculated by the area under the curve [from 0-24 hours] ratio of HR reduction and S -verapamil concentration) was significantly lower on day 21 (0.7 +/- 0.4 versus 1.2 +/- 0.7 [bpm]. [ng/mL](-1), for day 21 versus day 1; P <.01). CONCLUSIONS: In patients with chronic atrial fibrillation, clearance of oral, but not intravenous, S -verapamil and R -verapamil is significantly reduced with multiple doses compared with a single dose, thereby indicating predominant impairment of prehepatic rather than hepatic metabolism as the underlying mechanism. However, this kinetic change is clinically compensated by a decrease in the responsiveness to S -verapamil observed with regular dosing. The data suggest that despite accumulation of the drug individual verapamil doses can be maintained during long-term oral rate control therapy.
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