Chronopharmacokinetics of ethanol. I. Review of the literature and theoretical considerations.
Chronopharmacokinetics of ethanol. I. Review of the literature and theoretical considerations.
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乙醇的时间药代动力学。
DOI：
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发表时间：
1976
期刊：
影响因子：
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通讯作者：
Sturtevant Fm
中科院分区：
文献类型：
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作者：
Sturtevant Fm
虽然药物代谢和药物反应的昼夜变化是已知的，但药物动力学参数通常被认为是随着一天中的时间不变的。正如所提出的，时间药代动力学考虑了药代动力学参数的时间变异性的含义。为了研究一种物质的消失率的时间变化，从近似的线性过程到达到很低的血液水平。作为此类研究的背景，对乙醇的时辰药理学和乙醇血症的药代动力学的文献进行了综述。本文从理论上考虑了假想药物的消除常数随时间变化的规律，并遵循指数模型和零级模型。在描述这些情况时，提出了用正弦函数代替药物动力学微分方程式中的速率常数，并首次绘制了HERIN图。结论是：1)消除曲线中的节律性只能通过在不同的时间重复实验来确定；2)预期在一天中的一个时间估计的速率常数可能对一天中的另一个时间有效，这带有未知的风险。除非考虑参数的时辰药代动力学变化，否则任何药代动力学分析都不能被认为是确定的。
: Pharmacokinetic parameters are generally assumed to be invariate with the time of day, although circadian variation of drug metabolism and drug response is known. As proposed, chronopharmacokinetics considers the implications of the chronovariability of pharmacokinetic parameters. In order to investigate chronovariation in the rate of disappearance of a substance from the approximate a linear course until very low blood levels are attained. As a background for such studies, the literature on the chronopharmacologyof ethanol and the pharmacokinetics of ethanolemia is reviewed. Theoretical considerations are presented for chronovariation of elimination constants for hypothetical drugs following exponential and zero-order models. In describing these cases, the substitution of a sinusoidal function for the rate-constants in pharmacokinetic differential equations is proposed and graphed herin for the first time. It is concluded that: 1)rhythmicity within elimination curves can only be determined by repetion of the experiment at different times of the diel period; 2)the expectation that a rate-constant estimated at one time of the day may be valid for another part of the day carries with it an unknown risk. No pharmacokinetic analysis can be considered definitive unless chronopharmacokinetic variation of parameters is considered.