Asunto(s)
Antineoplásicos/farmacología , Tiosemicarbazonas/farmacología , Oligoelementos/farmacología , Animales , Carcinoma 256 de Walker , Línea Celular , Cobre/farmacología , Técnicas de Cultivo , Sinergismo Farmacológico , Masculino , Trasplante de Neoplasias , Ratas , Trasplante Homólogo , Zinc/farmacologíaAsunto(s)
Antígenos , Neoplasias , Fosfolípidos/análisis , Fosfolípidos/sangre , Animales , Reacciones Antígeno-Anticuerpo , Carcinoma 256 de Walker/inmunología , Carcinoma de Ehrlich/inmunología , Cromatografía en Papel , Glutamatos/análisis , Humanos , Leucemia Experimental , Hígado/análisis , Picratos/análisis , Ratas , Sarcoma Experimental , Espermina/análisis , Bazo/análisisRESUMEN
The metabolic chiral inversion of R-(-)-ibuprofen has been studied in human subjects by means of specific deuterium labeling and stereoselective gas chromatography-mass spectrometry methodology. After simultaneous p.o. administration of a mixture of R-(-)-ibuprofen (300 mg) and R-(-)-[3,3,3-2H3]ibuprofen (304 mg) to four adult male volunteers, the enantiomeric composition and deuterium content of the drug in serum, and of the drug and its principal metabolites in urine, were followed over a period of 24 hr. The results of these analyses indicated that: 1) conversion of R-(-)- to S-(+)-ibuprofen takes place with complete retention of deuterium at the beta-methyl (C-3) position; 2) chiral inversion of R-(-)-[2H3]ibuprofen is not subject to a discernible deuterium isotope effect; and 3) replacement of the beta-methyl hydrogen atoms by deuterium has no effect on any of the serum pharmacokinetic parameters for R-(-)- or S-(+)-ibuprofen. These data indicate that the process whereby R-(-)-ibuprofen undergoes metabolic inversion in human subjects does not involve 2,3-dehydroibuprofen as an intermediate, and that the underlying mechanism cannot, therefore, entail a desaturation/reduction sequence.