Clinical pharmacology studies of oltipraz--a potential chemopreventive agent.
Clinical pharmacology studies of oltipraz--a potential chemopreventive agent.
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潜在化学预防剂奥替普拉的临床药理学研究。
DOI：
10.1007/bf00944183
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发表时间：
1992
影响因子：
3.4
通讯作者：
Malone,W
中科院分区：
文献类型：
--
作者：
Dimitrov,NV;Bennett,JL;McMillan,J;Perloff,M;Leece,CM;Malone,W
使用不同剂量和时间表，对正常健康受试者进行了奥替普拉[4-甲基-5（吡嗪基-2）-1-2-二硫杂环戊烯-3-基）]的药理学研究。单次给药（1、2和3 mg/kg）导致血清（平均血清峰浓度分别为16、61和205 ng）和尿液中可检测到药物水平。t12较短（分别为4.4、4.1和5.3小时），每日多次给药12天后未达到稳态。当使用1.5和2.0 mg/kg/天时，在第一天引入负荷剂量产生稳态。每日给予奥替普拉可维持稳态，变化不显著。与低脂饮食相比，食用高脂肪饮食增加了奥替普拉的血清和尿液浓度（30-60%）。2例受试者在给药期间发生肠胃气胀。1例受试者出现拇指麻木和疼痛，出现类似亚急性心内膜炎中观察到的紫黑色小斑点。这些变化在停药后10天消失。奥替普拉治疗4周后，外周血细胞计数、生化特征或甲状腺功能试验均未观察到变化。需要对大量健康受试者进行进一步研究，以阐明小剂量奥替普拉长期给药的安全性和生物学疗效。
Pharmacological studies on Oltipraz [4-methyl-5(pyrazinyl-2)-1-2-dithiole-3-thione)] were conducted with normal healthy subjects using various doses and schedules. Administration of single doses (1, 2 and 3 mg/kg) resulted in detectable drug levels in the serum (mean peak serum concentrations 16, 61 and 205 ng, respectively) and urine. The t1/2was short (4.4, 4.1 and 5.3 hours respectively) and no steady state was achieved after multiple daily doses for 12 days. Introduction of a loading dose during the first day produced a steady state when 1.5 and 2.0 mg/kg/day were used. Daily administration of Oltipraz sustained the steady state with insignificant variations. Consumption of a high fat diet increased the serum and urine concentrations of Oltipraz (30–60%) compared to the low fat diet. Two subjects experienced flatulence during the administration of the drug. One subject developed numbness and pain in the thumbs with occurrence of small purplishblack spots resembling those observed in subacute endocarditis. These changes disappeared 10 days after discontinuation of the drug. No changes in peripheral blood counts, biochemical profile or thyroid function tests were observed after four weeks of Oltipraz. Further studies with a larger number of healthy subjects are needed for clarification of the safety and biological efficacy of small doses of Oltipraz during chronic administration.