title: Extensive oxidative metabolism of dextromethorphan in patients with almitrine neuropathy.
abstract: Almitrine bismesylate can induce a stereotypical sensory peripheral neuropathy probably through a toxic mechanism. High plasma concentrations of almitrine have been reported in a patient with neuropathy. Since large inter-individual variations in plasma drug concentrations are found it is possible that the development of toxicity may be linked to genetically determined polymorphic oxidation of the drug. Oxidation phenotyping was performed in fifteen patients with almitrine neuropathy using dextromethorphan, a test compound subject to oxidative metabolism similar to that of debrisoquine. All patients were of the extensive metaboliser phenotype. This result shows that, in contrast to perhexiline neuropathy, almitrine neuropathy is not related to slow oxidation of the compound with regard to the particular P-450 iso-enzyme involved in dextromethorphan and debrisoquine metabolism.
authors.affiliation: Département de Pathologie, Hôpital Henri Mondor, Créteil, France.
authors.forename: L
authors.initials: L
authors.lastname: Belec
authors.forename: D
authors.initials: D
authors.lastname: Larrey
authors.forename: H
authors.initials: H
authors.lastname: De Cremoux
authors.forename: M
authors.initials: M
authors.lastname: Tinel
authors.forename: F
authors.initials: F
authors.lastname: Louarn
authors.forename: D
authors.initials: D
authors.lastname: Pessayre
authors.forename: R
authors.initials: R
authors.lastname: Gherardi
mesh_terms: D000368:Aged; D015765:Almitrine; D003647:Debrisoquin / Q000378:metabolism; D003915:Dextromethorphan / Q000378:metabolism* / Q000652:urine; D005260:Female; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000139:chemically induced*; D006801:Humans; D007981:Levorphanol / Q000031:analogs & derivatives*; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects* / Q000097:blood
chemical_list: D010879:Piperazines; D007981:Levorphanol; D003915:Dextromethorphan; D015765:Almitrine; D003647:Debrisoquin