Volosov A, Bialer M
Department of Pharmaceutics, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Israel.
Biopharm Drug Dispos. 1999 Jan;20(1):3-9. doi: 10.1002/(sici)1099-081x(199901)20:1<3::aid-bdd146>3.0.co;2-7.
The goal of this study was to develop a new method, based on robust pharmacokinetic (PK) parameters, for determining t(max) (time of peak plasma concentration) and the magnitude of difference between the absorption (k(a)) and elimination (k) rate constants in the one compartment body model with first order input and output.
The function F(X) that describes the ratio of the AUC (area under the curve) from MRT (mean residence time) to infinity and the AUC from zero to MRT as a function of ratio between the first-order absorption and elimination constants (X) was derived and its limits were determined. Similarly, the function G(X) that describes the ratio between MRT and t(max) was derived and its limits were determined.
The functions F(X) and G(X) depend only on the ratio between k and k(a). Thus, the different values of the functions F(X) (a-values) and G(X) (b-values) were calculated as a function of the ratio k/k(a). A table with 1% increments of the relevant b-value for every a-value was derived. The appropriate t(max) was thus calculated from the quotient MRT and the relevant b-value. A useful application of the new method to a drug product with prolonged absorption and long half life was presented.
A new method that allows the calculation of t(max) and the k/k(a) ratio and derivation of a simple criterion of the equality between k and k(a) has been developed. This method is applicable to the one compartment open body model with first order absorption and elimination and is not based on single point parameters but on robust pharmacokinetic parameters such as AUC and MRT.
本研究的目标是开发一种基于稳健药代动力学（PK）参数的新方法，用于确定单室体内模型中具有一级输入和输出时的t(max)（血浆浓度峰值时间）以及吸收（k(a)）和消除（k）速率常数之间的差异幅度。
推导了描述从平均驻留时间（MRT）到无穷大的曲线下面积（AUC）与从零到MRT的AUC之比作为一级吸收和消除常数之比（X）的函数F(X)，并确定了其极限。同样，推导了描述MRT与t(max)之比的函数G(X)，并确定了其极限。
函数F(X)和G(X)仅取决于k与k(a)之比。因此，根据k/k(a)之比计算了函数F(X)（a值）和G(X)（b值）的不同值。得出了一个表格，其中每个a值对应的相关b值以1%的增量递增。因此，从MRT与相关b值的商计算出合适的t(max)。展示了该新方法在具有延长吸收和长半衰期的药物产品中的有用应用。
已开发出一种新方法，可计算t(max)和k/k(a)比值，并推导k与k(a)相等的简单标准。该方法适用于具有一级吸收和消除的单室开放体内模型，且不是基于单点参数，而是基于诸如AUC和MRT等稳健的药代动力学参数。
