口服vinorelbine药物动力学和绝对生物利用度研究实体肿瘤患者。

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马蒂,Fumoleau P,亚丁的,卢梭Y, Merrouche Y,罗比G,正在西纳克我,Puozzo C

口服vinorelbine药物动力学和绝对生物利用度研究实体肿瘤患者。

安11月杂志。2001;12 (11):1643 - 9。

PubMed ID

11822766 (在PubMed

]

文摘

背景:Vinorelbine hemisynthesis获得的长春花生物碱,使分子的亲脂性的比其他的长春花。一个注射配方已经销售用于治疗非小细胞肺癌(NSCLC)和晚期乳腺癌(ABC)。已研制出的一种新的口服形式及其登记的文件被提交。作为其发展的一部分,临床研究来确定口服vinorelbine管理的绝对生物利用度和药物动力学软胶囊胶囊,并评估其安全性与静脉管理。病人和方法:32例实体肿瘤患者纳入研究。患者禁食,并随机获得vinorelbine 1天,要么作为一个20分钟静脉(注射)注入25 mg / m2或软胶囊胶囊的剂量80毫克/平方米。患者治疗的替代路线一星期后冲洗。收集血液和尿液样本进行药代动力学分析在每个vinorelbine管理。安全评估后每个政府使用CALGB /扩展CTC分类。结果:24例符合药代动力学评价。 Oral vinorelbine was rapidly absorbed at 80 mg/m2 (Tmax 1.4 +/- 0.7 h) and showed a bioavailability of 43 +/- 14, and close to 40% based on AUC(last) and AUC(inf), respectively. A bioequivalence analysis was conducted on dosage-normalised blood exposures. Equivalence was demonstrated between 80 mg/m2 oral and 30 mg/m2 i.v., and between 60 mg/m2 oral and 25 mg/m2 i.v. The inter-individual variability was equivalent for both routes (CV: 38% and 39% for oral and i.v., respectively). A correlation was found in both methods between AUClast and % nadir variation in white blood cells (WBC) and polymorphonuclears (PMN). More cases of neutropenia (all grades pooled), leucopenia (grades 3-4 only) and nausea (grades 2-3) were induced by 80 mg/m2 oral vinorelbine than by 25 mg/m2 i.v. The greatest intensity of these effects, following oral administration, probably reflects the higher, observed drug exposure. CONCLUSION: At therapeutic dosage levels, pharmacokinetic behaviour and safety profiles were similar for both routes. The absolute bioavailability of the oral vinorelbine (new, soft gelatine capsule) was close to 40%. Inter-individual variability in drug exposure was equivalent in both routes. The pharmacokinetic/pharmacodynamic (PK/PD) relationship in haematological toxicity was independent of the routes of administration. Reliable, corresponding doses between oral and i.v. vinorelbine were established, which will result in bioequivalent AUC.

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药物

Vinorelbine