Sahnoun Z, Zhou X J, Bore P, Monjanel S, Favre R, Durand A, Rahmani R
INSERM U 278, faculté de pharmacie, institut Paoli-Calmettes, Marseilles, France.
Bull Cancer. 1990;77(11):1115-21.
Navelbine (NVB) (5'-noranhydrovinblastine) is a new semi-synthetic vincaalkaloid (VA) exhibiting a high affinity for tubulin and considerable anticancer activity in patients. A better hematologic tolerance and a weak neurotoxicity have been reported for this drug as compared to other VA. Moreover, NVB presents a relatively high bioavailability and a good digestive tolerance, thus offering original perspectives for the treatment of ambulatory cancer patients. A clinical pharmacokinetic study of NVB was carried out on 12 patients after oral administration of the drug. The pharmacokinetic parameters were similar to those of intravenous administration and also showed a high interindividual variability. Studies on the in vitro metabolism of NVB using hepatic microsomal fractions from 22 different donors demonstrated the formation of 3 metabolites. The biotransformation rate quantitatively varies from one human liver specimen to another, a fact which could be, in part, at the origin of the interindividual variability of the therapeutic response.
诺维本（NVB）（5'-去甲去氢长春碱）是一种新型半合成长春花生物碱（VA），对微管蛋白具有高亲和力，且在患者中具有显著的抗癌活性。与其他VA相比，该药物具有更好的血液学耐受性和较弱的神经毒性。此外，NVB具有相对较高的生物利用度和良好的消化耐受性，因此为门诊癌症患者的治疗提供了新的前景。对12例患者口服该药物后进行了NVB的临床药代动力学研究。药代动力学参数与静脉给药相似，且个体间差异较大。使用来自22个不同供体的肝微粒体组分对NVB进行体外代谢研究，结果显示形成了3种代谢产物。生物转化速率在不同人肝脏标本之间存在定量差异，这一事实可能部分是治疗反应个体间差异的原因。
