THE PHARMACOKINETICS OF 2.5-MG TO 10-MG ORAL DOSES OF MINOXIDIL IN HEALTHY-VOLUNTEERS
THE PHARMACOKINETICS OF 2.5-MG TO 10-MG ORAL DOSES OF MINOXIDIL IN HEALTHY-VOLUNTEERS
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DOI：
10.1002/j.1552-4604.1989.tb03307.x
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发表时间：
1989-02-01
影响因子：
2.9
通讯作者：
WRIGHT, CE
中科院分区：
文献类型：
--
作者：
FLEISHAKER, JC;ANDREADIS, NA;WRIGHT, CE
通过研究单次口服2.5、5.0和10.0 mg米诺地尔后的药代动力学，研究米诺地尔的剂量比例。该研究采用拉丁方交叉设计，在30名年轻、非肥胖、正常受试者中进行。治疗间隔4天洗脱期。采用高效液相色谱法（HPLC）和放射免疫法（RIA）测定血清和尿液中米诺地尔的浓度。在每个研究阶段监测仰卧位血压和脉搏。米诺地尔浓度测定RIA与HPLC测定的浓度高度相关，只有HPLC数据用于药代动力学分析。未观察到剂量标准化Cmax、tmax、分布容积、米诺地尔肾清除率或以米诺地尔或米诺地尔葡糖苷酸排泄的剂量百分比的显著影响。表观口服清除率、剂量标准化AUC和终末消除速率常数（β）在2.5 mg剂量和更高剂量之间观察到了这些参数，但5.0和10.0 mg剂量之间这些参数没有明显差异。因此，现有数据支持米诺地尔在此剂量范围内的剂量依赖性药代动力学。重复测量的方差分析发现，仰卧位血压和脉搏率的时间和治疗效果显着，但效果一般很小，临床意义不大。结果支持米诺地尔对血压正常者的血压影响很小的假设。
The dose proportionality of minoxidil was investigated by studying its pharmaockinetics after administration of single, oral doses of 2.5, 5.0, and 10.0 mg. The study, which was a Latin square cross-over design, was performed in 30 young, nonobese, normal subjects. Treatments were separated by a 4-day washout period. Serum and urine levels of minoxidil were determined by high-performance liquid chromatography (HPLC) and radioimmunoassay (RIA). Supine blood pressure and pulse were monitored during each study phase. Minoxidil concentrations determined by RIA were highly correlated with concentrations deermined by HPLC; only the HPLC data was used in the pharmacokinetic analyses. No significant effects were observed for dose normalized Cmax, tmax, volume of distribution, minoxidil renal clearance, or the percentage of the dose excreted as either minoxidil or minoxidil glucuronide. Significant differences in apparent oral clearance, dose normalized AUC, and terminal elimination rate constant (.beta.) were observed between the 2.5-mg dose and the higher doses, but no differences in these parameters between the 5.0- and 10.0-mg doses were apparent. Thus, the available data support dose-independent pharmacokinetics for minoxidil over this range of doses. Repeated measures analysis of variance detected significant time and treatment effects on supine blood pressure and pluse rate, but the effects were generally small and of little clinical significance. The results support the hypothesis that minoxidil has little effect on blood pressure in normotensive subjects.