Ebes F, McEwen J, De Vries M H, Raghoebar M
Department of Drug Disposition, Duphar B.V., Weesp. The Netherlands.
Eur J Drug Metab Pharmacokinet. 1991;Spec No 3:277-83.
The kinetics of idaverine was studied in an open, cross-over, partially randomized design after single oral (2 mg) and intravenous (1 and 2 mg doses to 12 healthy male subjects. In the first session, the volunteers were administered 1 mg idaverine by constant intravenous infusion during 45 min. The treatments in the second and third sessions were given according to a cross-over design, randomized in blocks of six for each session (2 mg either orally or by intravenous infusion during 45 min). The washout period between the sessions was at least 1 week. Plasma, urine and faeces were analysed for idaverine and its pharmacologically active metabolite N-desmethylidaverine by gas chromatography with nitrogen flame ionisation detection. After intravenous administration, the MRT was on average 2 hours and the mean CLS was about 900 ml.min-1. CLR is about twice the glomerular filtration rate, suggesting net tubular secretion of idaverine. The AUC and the cumulative urinary and faecal excretion values gave no indication of dose-disproportionality within the range of 1 and 2 mg administered intravenously. Maximum plasma levels of 1-3 ng.ml-1 were reached between 0.5 hours and 3 hours after oral dosing. The MRT was 4.4 hours. Systemic availability was about 29%. N-desmethylidaverine was barely detectable in plasma after all doses. Idaverine was well tolerated, only a small increase in heart rate was observed.
在一项开放、交叉、部分随机设计中，对12名健康男性受试者单次口服（2毫克）和静脉注射（1毫克和2毫克剂量）后，研究了伊达维林的药代动力学。在第一阶段，志愿者在45分钟内通过持续静脉输注给予1毫克伊达维林。第二和第三阶段的治疗按照交叉设计进行，每次给药以6人为一组随机分组（2毫克，口服或在45分钟内静脉输注）。各阶段之间的洗脱期至少为1周。通过带有氮火焰离子化检测的气相色谱法分析血浆、尿液和粪便中的伊达维林及其药理活性代谢物N-去甲基伊达维林。静脉给药后，平均滞留时间为2小时，平均清除率约为900毫升·分钟⁻¹。肾清除率约为肾小球滤过率的两倍，提示伊达维林存在肾小管净分泌。在静脉注射1毫克和2毫克剂量范围内，曲线下面积以及累积尿排泄和粪排泄值均未显示剂量不成比例。口服给药后0.5小时至3小时之间达到的最大血浆浓度为1 - 3纳克·毫升⁻¹。平均滞留时间为4.4小时。全身生物利用度约为29%。所有剂量给药后，血浆中几乎检测不到N-去甲基伊达维林。伊达维林耐受性良好，仅观察到心率略有增加。
