Byron P R, Notari R E
J Pharm Sci. 1976 Aug;65(8):1140-4. doi: 10.1002/jps.2600650804.
Computer simulations were used to examine the effect of first-order absorption on the disposition of one- and two-compartment model drugs. Two-compartment systems that attain a clinically acceptable beta-phase after rapid intravenous injection were perturbed by introduction of drug via first-order absorption. The validity of perceiving such a system as a potential "flip-flop" model was tested by comparing the negative slopes of log-linear plasma-time profiles to known values for ka and beta for various values of ka, k12, k21, and k10. Although most log-linear plots showed excellent correlation coefficients (r2 greater than 0.996), their negative slopes (S) did not represent either ka or beta under various combinations. A similar consideration of the one-compartment model enabled a comparison to be made between the two systems. Maximum negative errors were observed for both one- and two-compartment drugs as ka leads to k2 or beta, respectively. The value for S provided a good estimate of the absorption rate constant, ka, when k2 greater than or equal 2ka (one compartment) or beta greater than or equal 2ka. The elimination rate constant (k2 or beta) could be obtained from S for all one-compartment and some two-compartment drugs when the value of ka was approximately twice that of k2 or beta. Large positive errors also were observed with certain two-compartment drugs where the ratio of the four rate constants apparently linearized a nonlinear plasma profile. Conditions wherein S may be expected to approach beta wherein S approaches ka are clearly defined.
采用计算机模拟研究一级吸收对单室和双室模型药物处置的影响。在快速静脉注射后达到临床可接受的β相的双室系统，通过一级吸收引入药物而受到干扰。通过比较对数线性血药浓度-时间曲线的负斜率与不同ka、k12、k21和k10值下已知的ka和β值，来检验将这样一个系统视为潜在“翻转”模型的有效性。尽管大多数对数线性图显示出极好的相关系数（r2大于0.996），但在不同组合下，它们的负斜率（S）既不代表ka也不代表β。对单室模型进行类似的考量，可以对这两个系统进行比较。当ka分别导致k2或β时，单室和双室药物均观察到最大负误差。当k2大于或等于2ka（单室）或β大于或等于2ka时，S值能很好地估计吸收速率常数ka。当ka值约为k2或β的两倍时，对于所有单室药物和一些双室药物，可从S获得消除速率常数（k2或β）。对于某些双室药物，当四个速率常数的比值明显使非线性血药浓度曲线线性化时，也观察到较大的正误差。明确界定了S可能接近β以及S接近ka的条件。
