Zhou X J, Landi H, Breillout F, Rahmani R
INSERM U278, Faculté de Pharmacie, Marseille, France.
Anticancer Drugs. 1993 Aug;4(4):511-5. doi: 10.1097/00001813-199308000-00014.
Navelbine (NVB) pharmacokinetics has been investigated in the dog after p.o. administration of increasing doses (0.5-8 mg/kg) and in the monkey after a single dose of 40 mg/ml. In the dog, NVB pharmacokinetic parameters, Cmax, tmax, AUC, t1/2 and Cl, were 49.0-1021.0 ng/ml, 1.14-3.69 h, 370.0-11754.5 ng/ml h, 19.3-64.3 h and 0.46-1.47 l/h/kg, respectively. As the dose increased, the plasma concentration peak appeared more slowly and t1/2 increased significantly with a marked reduction in Cl. Moreover, NVB pharmacokinetics in the dog exhibited significant dose-dependency as demonstrated by analysis of variance (ANOVA) of dose-normalized AUC and Cmax. Pharmacokinetic parameters estimated from monkey data were essentially the same as those of the dog (Cmax, 877.6 mg/ml; tmax, 1.14 h; AUC, 7004.8 ng/ml h; t1/2, 18.2 h) except for Cl (10.40 l/h/kg), which was about 10-fold that of the dog.
已对犬口服递增剂量（0.5 - 8毫克/千克）后的诺维本（NVB）药代动力学进行了研究，并对猴单次给予40毫克/毫升后的药代动力学进行了研究。在犬中，NVB的药代动力学参数Cmax、tmax、AUC、t1/2和Cl分别为49.0 - 1021.0纳克/毫升、1.14 - 3.69小时、370.0 - 11754.5纳克/毫升·小时、19.3 - 64.3小时和0.46 - 1.47升/小时/千克。随着剂量增加，血浆浓度峰值出现得更慢，t1/2显著增加，Cl显著降低。此外，通过对剂量标准化的AUC和Cmax进行方差分析（ANOVA）表明，犬体内的NVB药代动力学呈现出显著的剂量依赖性。从猴的数据估算的药代动力学参数与犬基本相同（Cmax，877.6毫克/毫升；tmax，1.14小时；AUC，7004.8纳克/毫升·小时；t1/2，18.2小时），但Cl（10.40升/小时/千克）除外，其约为犬的10倍。
