BILIARY ELIMINATION AND PHARMACOKINETICS OF VINORELBINE IN MICROPIGS

The biliary elimination and pharmacokinetics of vinorelbine (NVB) were investigated in five conscious micropigs provided with a double-termi nal choledocal fistula allowing the collection and reinstillation of b ile. After the i. v. administration of NVB (0.5 mg/kg), serum and bile samples were collected over a 48-h period. The concentrations of NVB were measured by high-performance liquid chromatography. The serum con centrations decreased rapidly from a maximal value of 208.6 ng/ml (SD, 111.7 ng/ml). The mean half-life was 10.9 h (SD, 8.6 h) and the mean AUC0-48 h was 292.8 ng ml-1 h (SD, 79.4 ng ml-1 h). The bile concentra tions were high, amounting to 16.0 mug/ml (range, 5.4-27.7 mug/ml). Th e 0- to 48-h biliary excretion of unchanged NVB accounted for 25.8% (S D, 5.7%) of the injected dose, with 21.5% (SD, 4.0%) being eliminated during the 0- to 8-h period. Desacetyl-NVB was found in an inconstant manner and in very low amounts in bile samples. In addition, no glucur onide of NVB could be detected. Thus, in the micropig, biliary excreti on represents an important route of elimination for NVB.