Pharmacokinetics of navelbine after oral administration in the dog and the monkey.
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.
INSERM U278, Faculté de Pharmacie, Marseille, France.
X J
XJ
Zhou
H
H
Landi
F
F
Breillout
R
R
Rahmani
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000097:blood / Q000493:pharmacokinetics*; D004285:Dogs / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008253:Macaca mulatta / Q000378:metabolism*; D008297:Male; D014747:Vinblastine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D000077235:Vinorelbine
D000970:Antineoplastic Agents; D014747:Vinblastine; D000077235:Vinorelbine