The clinical pharmacokinetics of vinorelbine (Navelbine).

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