Cheng H, Jusko W J
Department of Drug Metabolism, Merck Research Laboratories, West Point, Pennsylvania 19486.
Pharm Res. 1993 Jan;10(1):8-13. doi: 10.1023/a:1018904509178.
Equations for the mean residence times in the body (MRT) and AUMC/AUC of a drug and its metabolite have been derived for an oral drug undergoing first-pass and linear reversible metabolism. The mean residence times of the drug or interconversion metabolite in the body after oral drug are described by equations which include the mean absorption time (MAT), the mean residence times of the drug or metabolite in the body after intravenous administration of the drug, the fractions of the dose entering the systemic circulation as the parent drug and metabolite, and the systemically available fractions of the drug (Fpp) or metabolite (Fpm). Similarly, the AUMC/AUC of the drug and metabolite after oral drug can be related to the MAT, ratios of the fraction of the dose entering the systemic circulation to the systemically available fraction, the first-time fractional conversion of each compound, and AUMC/AUC ratios after separate intravenous administration of each compound. The Fpp and Fpm values, in turn, are related to the first-pass availabilities of both drug and metabolite and the first-time fractional conversion fractions. The application of these equations to a dual reversible two-compartment model is illustrated by computer simulations.
对于经历首过效应和线性可逆代谢的口服药物，已推导得出药物及其代谢物在体内的平均驻留时间（MRT）以及AUMC/AUC的方程。口服药物后，药物或相互转化代谢物在体内的平均驻留时间由包含平均吸收时间（MAT）、静脉注射药物后药物或代谢物在体内的平均驻留时间、以母体药物和代谢物形式进入体循环的剂量分数以及药物（Fpp）或代谢物（Fpm）的全身可利用分数的方程来描述。同样，口服药物后药物和代谢物的AUMC/AUC可与MAT、进入体循环的剂量分数与全身可利用分数的比值、每种化合物的首次分数转化率以及每种化合物单独静脉注射后的AUMC/AUC比值相关。反过来，Fpp和Fpm值与药物和代谢物的首过效应以及首次分数转化分数有关。通过计算机模拟说明了这些方程在双可逆二室模型中的应用。
