Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Médicament, Paris, France) is a semisynthetic vinca alkaloid agent that has been structurally modified on the catharanthine nucleus to impart increased lipophilicity. As a result, vinorelbine appears to possess a higher therapeutic index and different pharmacokinetic properties from other marketed vinca alkaloids. Vinorelbine has been quantified in biologic matrices by measurement of total radioactivity, radioimmunoassay, and high-performance liquid chromatography. Because it is specific for the parent drug, high-performance liquid chromatography has generated the most reliable pharmacokinetic data. Vinorelbine is highly bound to platelets and lymphocytes, and is also bound to alpha 1-acid glycoprotein, albumin, and lipoproteins. The drug undergoes significant metabolism and elimination via the liver and metabolites are excreted primarily in the bile. Two likely vinorelbine metabolites, vinorelbine N-oxide and deacetylvinorelbine, have been isolated and identified in human urine and very low concentrations appeared in plasma. Urinary excretion of unchanged drug accounts for less than 20% of an intravenous dose, with fecal elimination accounting for an additional 30% to 60%. The pharmacokinetic profile of vinorelbine after intravenous bolus or infusion is characterized by triexponential decay. Initial rapid decay is due primarily to distribution into tissues in the peripheral compartments. There is a prolonged terminal phase due to relatively slow efflux of the drug from peripheral compartments, which results in a long terminal phase half-life, with average values ranging from 27.7 to 43.6 hours. Plasma clearance of vinorelbine is high, approaching hepatic blood flow in humans, and its volume of distribution is large, indicating extensive extravascular distribution. In comparison to vinblastine or vincristine, vinorelbine has a higher clearance and a larger volume of distribution than either drug, and a half-life shorter than vinblastine but longer than vincristine. There is no relationship between the age of the patient and the pharmacokinetic parameters of vinorelbine, and coadministration of cisplatin does not appear to influence the pharmacokinetics of vinorelbine. Vinorelbine is the first vinca alkaloid to show promising efficacy following oral administration, and this has led to the development of a liquid-filled, soft-gelatin capsule dosage form. The absolute bioavailability of vinorelbine from this dosage form was 27% when intravenous doses of 30 mg/m2 were compared with oral doses of 100 mg/m2.