Henthorn T K, Avram M J, Krejcie T C
Department of Anesthesia, Northwestern University Medical School, Chicago, Illinois 60611.
Anesthesiology. 1989 Nov;71(5):635-9. doi: 10.1097/00000542-198911000-00002.
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.
由于已证明阿芬太尼在体外可抑制异喹胍羟化酶，且所报道的阿芬太尼消除清除率存在相当大的变异性，因此研究了异喹胍代谢表型对阿芬太尼消除清除率的可能影响。在对四名异喹胍广泛代谢者和三名异喹胍代谢不良者快速静脉给药后，测定了阿芬太尼的处置情况。使用尿右美沙芬/右啡烷代谢比率试验确定异喹胍羟化表型。阿芬太尼的处置情况用三室开放乳头体模型进行表征。尽管七名志愿者的代谢比率范围近700倍，但右美沙芬/右啡烷代谢比率与阿芬太尼的消除清除率之间并无关联。这表明阿芬太尼消除清除率的变异性并非由于异喹胍羟化酶的多态性所致。这种变异性也不是由于肝血流量变化引起的，因为在本研究中阿芬太尼清除率与吲哚菁绿清除率无关。
