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静脉注射和口服给药后血药浓度或血浆浓度-时间曲线下面积之比的通用方程及其在药物消除个体间差异中的应用。

A general equation for the ratio of the areas below the blood or plasma concentration time-curves following intravenous and oral drug administration and its application to inter-subject variations in drug elimination.

作者信息

Vaughan D P, Trainor A

出版信息

Br J Clin Pharmacol. 1975 Jun;2(3):239-50. doi: 10.1111/j.1365-2125.1975.tb01582.x.

DOI:10.1111/j.1365-2125.1975.tb01582.x
PMID:1234504
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1402568/
Abstract

1 When a drug is metabolized in the liver the total area under the plasma or blood concentration-time curve following oral drug administration is less than the area obtained after intravenous drug administration. This difference has been termed the 'first-pass effect'. 2 General equations for the areas below the blood or plasma concentration-time curve of a drug following intravenous and oral drug administration are derived. 3 An explicit expression for the ratio of areas below the blood or plasma concentration-time curves following intravenous and oral drug administration is derived. 4 By the application of the derived equations it is shown that the relative contribution of hepatic drug metabolism and urinary excretion to inter-subject variation in drug elimination can be easily ascertained.

摘要
  1. 当一种药物在肝脏中代谢时,口服给药后血浆或血液浓度-时间曲线下的总面积小于静脉给药后获得的面积。这种差异被称为“首过效应”。2. 推导了药物静脉给药和口服给药后血液或血浆浓度-时间曲线下面积的一般方程。3. 推导了静脉给药和口服给药后血液或血浆浓度-时间曲线下面积之比的显式表达式。4. 通过应用推导的方程表明,可以很容易地确定肝脏药物代谢和尿液排泄对药物消除个体间差异的相对贡献。

相似文献

1
A general equation for the ratio of the areas below the blood or plasma concentration time-curves following intravenous and oral drug administration and its application to inter-subject variations in drug elimination.静脉注射和口服给药后血药浓度或血浆浓度-时间曲线下面积之比的通用方程及其在药物消除个体间差异中的应用。
Br J Clin Pharmacol. 1975 Jun;2(3):239-50. doi: 10.1111/j.1365-2125.1975.tb01582.x.
2
Model independent derivation of general equations for the "first-pass" effect and extra-hepatic drug elimination.“首过”效应和肝外药物消除通用方程的模型无关推导。
Eur J Clin Pharmacol. 1977;11(1):57-64. doi: 10.1007/BF00561789.
3
A general model of metabolite kinetics following intravenous and oral administration of the parent drug.母体药物静脉注射和口服给药后代谢物动力学的一般模型。
Biopharm Drug Dispos. 1988 Mar-Apr;9(2):159-76. doi: 10.1002/bod.2510090205.
4
A convenient method for estimating the quantity of drug eliminated by the routes other than hepatic metabolism and renal excretion and the fraction of drug that reaches the "first pass" after oral administration.一种用于估算经肝代谢和肾排泄以外途径消除的药物量以及口服给药后到达“首过”的药物分数的简便方法。
J Pharm Sci. 2006 Apr;95(4):828-33. doi: 10.1002/jps.20479.
5
First-pass elimination. Basic concepts and clinical consequences.首过消除。基本概念及临床后果。
Clin Pharmacokinet. 1984 Jan-Feb;9(1):1-25. doi: 10.2165/00003088-198409010-00001.
6
Route of administration and drug metabolism.给药途径与药物代谢。
Eur J Pharmacol. 1972 Sep;19(3):323-9. doi: 10.1016/0014-2999(72)90098-2.
7
Estimation of area under the curve for drugs subject to enterohepatic cycling.对经历肠肝循环的药物的曲线下面积的估算。
J Pharmacokinet Biopharm. 1985 Dec;13(6):589-608. doi: 10.1007/BF01058903.
8
The influence of drug kinetics in blood on the calculation of oral bioavailability in linear pharmacokinetics: the traditional equation may considerably overestimate the true value.线性药代动力学中血液药物动力学对口服生物利用度计算的影响:传统公式可能会显著高估真实值。
J Pharm Sci. 2006 Apr;95(4):834-48. doi: 10.1002/jps.20570.
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Drug metabolite concentration-time profiles: influence of route of drug administration.药物代谢物浓度-时间曲线:给药途径的影响
Br J Clin Pharmacol. 1984 Apr;17(4):385-94. doi: 10.1111/j.1365-2125.1984.tb02362.x.
10
The ratio of first to zeroth moments of the plasma profile of an oral drug undergoing first-pass and linear reversible metabolism.
Biopharm Drug Dispos. 1995 Dec;16(9):791-6. doi: 10.1002/bdd.2510160908.

引用本文的文献

1
Applications of a recirculatory stochastic pharmacokinetic model: limitations of compartmental models.循环随机药代动力学模型的应用:房室模型的局限性
J Pharmacokinet Biopharm. 1979 Apr;7(2):207-25. doi: 10.1007/BF01059739.
2
Estimating reduced availability due to first pass elimination from relative total clearance and renal clearance.
Eur J Clin Pharmacol. 1988;35(4):397-400. doi: 10.1007/BF00561371.
3
A model-independent proof of Dost's law of corresponding areas.多斯特对应面积定律的一个与模型无关的证明。
J Pharmacokinet Biopharm. 1977 Jun;5(3):271-6. doi: 10.1007/BF01065400.
4
Model independent derivation of general equations for the "first-pass" effect and extra-hepatic drug elimination.“首过”效应和肝外药物消除通用方程的模型无关推导。
Eur J Clin Pharmacol. 1977;11(1):57-64. doi: 10.1007/BF00561789.

本文引用的文献

1
Influence of the route of administration on the area under the plasma concentration-time curve.给药途径对血浆浓度-时间曲线下面积的影响。
J Pharm Sci. 1969 Jan;58(1):71-5. doi: 10.1002/jps.2600580114.
2
Concept of a volume of distribution and possible errors in evaluation of this parameter.分布容积的概念以及该参数评估中可能存在的误差。
J Pharm Sci. 1968 Jan;57(1):128-33. doi: 10.1002/jps.2600570125.
3
Influence of first-pass effect on availability of drugs on oral administration.首过效应对口服给药时药物可利用度的影响。
J Pharm Sci. 1971 Sep;60(9):1338-40. doi: 10.1002/jps.2600600909.
4
Oral absorption and disposition kinetics of lidocaine hydrochloride in dogs.盐酸利多卡因在犬体内的口服吸收及处置动力学
J Pharmacol Exp Ther. 1970 Jul;174(1):1-8.
5
Steady-state plasma levels of nortriptyline in twins: influence of genetic factors and drug therapy.双胞胎中去甲替林的稳态血浆水平:遗传因素和药物治疗的影响。
Br Med J. 1969 Dec 27;4(5686):764-8. doi: 10.1136/bmj.4.5686.764.
6
Pharmacokinetics of pentazocine in the rhesus monkey.
J Pharm Sci. 1974 Jan;63(1):84-8. doi: 10.1002/jps.2600630121.
7
An analysis of the inter-subject variation in the metabolism of pentazocine.喷他佐辛代谢的个体间差异分析。
J Pharm Pharmacol. 1974 Oct;26(10):789-98. doi: 10.1111/j.2042-7158.1974.tb09175.x.