[Clinical pharmacokinetics of navelbine after oral administration, in vitro metabolism and interindividual variability]

Bull Cancer. 1990;77(11):1115-21.
[Article in French]

Abstract

Navelbine (NVB) (5'-noranhydrovinblastine) is a new semi-synthetic vincaalkaloid (VA) exhibiting a high affinity for tubulin and considerable anticancer activity in patients. A better hematologic tolerance and a weak neurotoxicity have been reported for this drug as compared to other VA. Moreover, NVB presents a relatively high bioavailability and a good digestive tolerance, thus offering original perspectives for the treatment of ambulatory cancer patients. A clinical pharmacokinetic study of NVB was carried out on 12 patients after oral administration of the drug. The pharmacokinetic parameters were similar to those of intravenous administration and also showed a high interindividual variability. Studies on the in vitro metabolism of NVB using hepatic microsomal fractions from 22 different donors demonstrated the formation of 3 metabolites. The biotransformation rate quantitatively varies from one human liver specimen to another, a fact which could be, in part, at the origin of the interindividual variability of the therapeutic response.

Publication types

  • Clinical Trial

MeSH terms

  • Administration, Oral
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / metabolism
  • Antineoplastic Agents / pharmacokinetics*
  • Drug Evaluation
  • Female
  • Humans
  • Male
  • Microsomes, Liver / metabolism
  • Middle Aged
  • Neoplasms / metabolism
  • Otorhinolaryngologic Neoplasms / drug therapy*
  • Radioimmunoassay
  • Vinblastine / administration & dosage
  • Vinblastine / analogs & derivatives*
  • Vinblastine / metabolism
  • Vinblastine / pharmacokinetics
  • Vinorelbine

Substances

  • Antineoplastic Agents
  • Vinblastine
  • Vinorelbine