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半胱氨酸对绿猴(埃塞俄比亚猕猴)中奥替普拉血药浓度的影响。

Effect of cysteine on oltipraz blood levels in green monkeys (Cercopithecus aethiops).

作者信息

Ali H M, Sulaiman S M, Bennett J L, Homeida M M

出版信息

Chemotherapy. 1984;30(4):255-61. doi: 10.1159/000238277.

Abstract

Oral coadministration of oltipraz, an antischistosomal compound, with cysteine to green monkeys (Cercopithecus aethiops) led to a marked increase in both the extent and rate of oltipraz bioavailability. The drug blood levels were monitored using a single extraction gas-liquid chromatographic assay. When 6 healthy adult animals were given oltipraz together with cysteine in a crossover study, peak serum concentrations, areas under the curve and absorption rate constants of oltipraz were on average 7 times greater than when the drug was administered alone. Oltipraz peak serum concentrations were reached 1 h earlier as a result of cysteine administration (2 h after dosing). At present, the mechanisms responsible for the effect(s) of cysteine on oltipraz bioavailability have not been identified. The marked increase in oltipraz bioavailability produced by coadministration of cysteine, irrespective of the exact mechanisms involved, may have significant clinical implications with regard to the treatment of schistosomiasis. Our results also indicate that oltipraz blood levels seem to be influenced by some sex-related factors. Male monkeys had higher oltipraz blood levels than females. These sex-induced differences were more evident in oltipraz-cysteine-treated monkeys.

摘要

将抗血吸虫化合物奥替普拉与半胱氨酸联合口服给予绿猴(非洲绿猴),导致奥替普拉的生物利用度在程度和速率上均显著增加。使用单次萃取气液色谱分析法监测药物血药浓度。在一项交叉研究中,当给6只健康成年动物同时给予奥替普拉和半胱氨酸时,奥替普拉的血清峰值浓度、曲线下面积和吸收速率常数平均比单独给药时高7倍。由于给予半胱氨酸,奥替普拉血清峰值浓度提前1小时达到(给药后2小时)。目前,尚未确定半胱氨酸对奥替普拉生物利用度产生影响的机制。无论涉及的确切机制如何,联合给予半胱氨酸所导致的奥替普拉生物利用度显著增加,可能对血吸虫病的治疗具有重要的临床意义。我们的结果还表明,奥替普拉的血药浓度似乎受一些与性别相关的因素影响。雄性猴子的奥替普拉血药浓度高于雌性。这些性别差异在接受奥替普拉 - 半胱氨酸治疗的猴子中更为明显。

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