PHARMACOKINETICS OF ORAL NOSCAPINE
PHARMACOKINETICS OF ORAL NOSCAPINE
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DOI：
10.1007/bf00315110
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发表时间：
1990-01-01
影响因子：
2.9
通讯作者：
ALM, AT
中科院分区：
文献类型：
--
作者：
KARLSSON, MO;DAHLSTROM, B;ALM, AT
在一项四向交叉研究中，对20名健康志愿者服用100 mg、200 mg和300 mg那可丁片剂和200 mg溶液的相对生物利用度进行了评估，重复给予200 mg剂量，以评估个体内变异性。诺斯卡品片剂的AUC增加不成比例，因为剂量增加3倍导致AUC增加9倍。这种剂量依赖性可能主要归因于药物的饱和首过代谢。 与相应剂量的片剂相比，以溶液形式给予那可卡品在较早时间点的最大浓度显著更高，AUC更高。在第二次给药时，重复给予诺斯卡品片剂和溶液产生较高的AUC。没有发现这种遗留效应的原因，剩余的那可丁的贡献可以忽略不计。那可丁的终末半衰期为4.5小时，与制剂或剂量大小无关。诺斯卡品动力学的个体间和个体内变异性都非常高，例如200 mg片剂AUC的CV分别为73%和51%。
The relative bioavailability in 20 healthy volunteers of 100 mg, 200 mg and 300 mg tablets of noscapine and 200 mg as a solution has been assessed in a four-way cross-over study, with repeated administration of the 200 mg dose to assess intraindividual variability. There was a disproportionate increase in the AUC of noscapine tablets, as a 3-fold increase in dose produced a 9-fold rise in AUC. This dose-dependency could mainly be attributed to saturable first-pass metabolism of the drug. Administration of noscapine as a solution resulted in a significantly higher maximal concentration at an earlier time-point and a higher AUC than the corresponding dose as tablets. Repeated administration of noscapine tablets and solution yielded higher AUC on the second dosing occasion. No cause for this carry-over effect was found, and the contribution of remaining noscapine was negligible. The terminal half-life of noscapine, which was independent of formulation or dose size was 4.5 h. Both inter- and intraindividual variability in noscapine kinetics were very high, e.g. 73% and 51% CV of the AUC for the 200 mg tablet.