ABSTRACT
The polymorphic oxidative metabolism of debrisoquine and sparteine were discovered in the seventies by Mahgoub and Eichelbaum. Since then, many other therapeutic substances were added and one of these drugs is dextromethorphan. The object of this investigation was to ascertain the distribution of the oxidative phenotype of dextromethorphan in the Uruguayan population. The drug and its metabolite, dextrorphan, were quantified in the urine of 165 healthy volunteers by a modificacion of an HPLC method by Chen et al. The metabolic ratio was calculated and frequency distribution histograms were drawn. By inspection of the histogram two antimodes can be assigned which determine three sub-populations: on one side the fast extensive metabolizers (n = 30, 18.2 per cent), in the middle the extensive metabolizers (n = 123, 74.5 per cent) and on the other extreme of the histogram the slow metabolizers (n = 12, 7.3 per cent). No other studies have confirmed thus far this trimodal distribution. This research will be continued by genotyping the populations studied in order to confirm these findings and to elucidate the underlying genetic mechanisms of the polymorphism.
Subject(s)
Humans , Male , Female , Adult , Dextromethorphan/urine , Dextrorphan/urine , Enzymes/genetics , Oxidoreductases, O-Demethylating/metabolism , Polymorphism, Genetic , Phenotype , UruguayABSTRACT
Es de interés para el farmacólogo clínico general el estudio de los factores genéticos que determinan la respuesta a los medicamentos. El polimorfismo genético de la debrisoquina/sparteína ha sido descrito en la década del 70 y ha tomado gran relevancia dado que un número significativo de fármacos utilizados en terapéutica clínica se oxidan por la misma vía metabólica que éstos. El dextrometorfan es un antitusígeno que cosegrega con la debrisoquina y su uso es más seguro. En el presente estudio se caracterizó la distribución de la O-demetilación del dextrometorfan en la población uruguaya (fenotipificación) mediante el cociente metabólico (CM). El objetivo del estudio fue conocer el comportamiento farmacogenético de nuestra población para esta vía metabólica. Se fenotipificaron 165 voluntarios en condiciones basales y se encontró un 6,3 por ciento de metabolizadores lentos. El histograma de frecuencia del CM muestra algunas peculiaridades que se discuten en el texto