Alfentanil Clearance is Independent of the Polymorphic Debrisoquin Hydroxylase

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Abstract
Because alfentanil has been shown to inhibit debrisoquin hydroxylase in vitro, and there is considerable variability in the reported elimination clearance of alfentanil, the possible influence of the debrisoquin metabolic phenotype on the elimination clearance of alfentanil was studied. The disposition of alfentanil was determined after rapid intravenous administration to four extensive debrisoquin metabolizers and three poor debrisoquin metabolizers. Debrisoquin hydroxylation phenotype was determined using the urinary dextromethorphan/dextrorphan metabolic ratio test. The disposition of alfentanil was characterized by a three-compartment open mammillary model. There was no relationship between the dextromethorphan/dextrorphan metabolic ratio and the elimination clearance of alfentanil despite a nearly seven hundred-fold range of the metabolic ratio in the seven volunteers. This indicates that the variability in the elimination clearance of alfentanil is not due to the polymorphism of debrisoquin hydroxylase. Nor is this variability due to variable hepatic blood flow because in this study alfentanil clearance was not related to indocyanine green clearance.