RESUMEN
1. Almitrine bismesylate displays wide inter-subject variation in peak plasma concentrations and can induce peripheral polyneuropathy. 2. The phenotyped volunteer panel approach was used to examine whether almitrine oxidation displayed a genetic polymorphism of the debrisoquine/sparteine type. 3. There was no difference between poor and extensive metabolisers of debrisoquine with respect to the pharmacokinetics and metabolism of almitrine.
Asunto(s)
Almitrina/metabolismo , Debrisoquina/metabolismo , Esparteína/metabolismo , Adulto , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Masculino , Oxidación-Reducción , Fenotipo , Polimorfismo GenéticoRESUMEN
Rats showing an ataxic gait induced by 20 wk of treatment with 0, 30, or 60 mg/kg of difluorobenzhydrylpiperadine (DFBP), a detriazinyl metabolic of almitrine, were examined by light microscopy and transmission electron microscopy. Vacuolar degeneration associated with lamellar inclusions was observed in musculus soleus and m. interossei of the hindlimbs in DFBP-treated rats. The inclusions were also produced within sensory neurons, satellite and Schwann cells, and vascular endothelial cells of thoracic and lumbar dorsal root ganglia as well as muscle spindles of affected muscles. Membrane-bound vacuoles containing electron-dense granules were seen in the peripheral nerves. This study demonstrated neuronal and muscular toxicity of DFBP in rats.