Karol M D, Goodrich S
Department of Pharmaceutical Sciences, College of Pharmacy, University of Arizona, Tucson 85721.
Pharm Res. 1988 Jun;5(6):347-51. doi: 10.1023/a:1015951426191.
A two-step analytic procedure to determine the rate and extent of metabolite production following administration of the parent compound is described. The procedure provides the rate and extent of metabolite production as a function of time by application of the general model independent approach of deconvolution. The metabolite unit impulse response function is obtained by implicit deconvolution of the metabolite data with a truncated constant-rate metabolite input function. Then the obtained unit impulse response function is used in an analytic deconvolution with metabolite data following administration of the parent compound to obtain the rate and extent of metabolite production. The input function is also deconvolved with metabolite data to obtain the unit impulse response function appropriate for prediction of metabolite levels given a selected input of parent compound. The expected profile following administration of the consecutive infusions of parent drug is shown for both parent and metabolite. The rationale for selection of deconvolution methods is discussed. The approach is applied to data for procainamide and N-acetylprocainamide from three human subjects. The results indicate that from 27 to 39% of the procainamide was converted to N-acetylprocainamide in these subjects.
本文描述了一种两步分析程序，用于确定母体化合物给药后代谢产物生成的速率和程度。该程序通过应用反卷积的通用模型无关方法，将代谢产物生成的速率和程度表示为时间的函数。代谢产物单位脉冲响应函数通过将代谢产物数据与截断的恒定速率代谢产物输入函数进行隐式反卷积获得。然后，将获得的单位脉冲响应函数用于与母体化合物给药后的代谢产物数据进行解析反卷积，以获得代谢产物生成的速率和程度。输入函数也与代谢产物数据进行反卷积，以获得在选定母体化合物输入情况下适合预测代谢产物水平的单位脉冲响应函数。展示了连续输注母体药物后母体和代谢产物的预期曲线。讨论了选择反卷积方法的基本原理。该方法应用于来自三名人类受试者的普鲁卡因胺和N-乙酰普鲁卡因胺的数据。结果表明，在这些受试者中，27%至39%的普鲁卡因胺转化为N-乙酰普鲁卡因胺。
