IDENTIFIABLE PHARMACOKINETIC MODELS - THE ROLE OF EXTRA INPUTS AND MEASUREMENTS
IDENTIFIABLE PHARMACOKINETIC MODELS - THE ROLE OF EXTRA INPUTS AND MEASUREMENTS
复制标题
DOI：
10.1007/bf01060058
复制
发表时间：
1980-01-01
期刊：
影响因子：
--
通讯作者：
BROWN, RF
中科院分区：
文献类型：
--
作者：
GODFREY, KR;JONES, RP;BROWN, RF
单输入、单输出实验可能导致用于描述药代动力学的线性房室模型的速率常数的非唯一解。在存在有限数量的解的情况下，必须使用先验知识来区分解。当有无穷多个解时，必须对某些速率常数的值进行假设，以便获得其他速率常数的唯一解。考虑这样的实验，并且确定添加额外输入（与第一输入同时）或进行额外测量是否会导致唯一解。扰动第二个输入显然是有用的，但只有当扰动的形状与第一个输入不同时。尿液中的药物和血浆中的代谢物的测量通常无助于解决药物动力学模型的可识别性。如果使用放射性示踪剂，则第二次测量（例如，通过外部扫描肝脏的放射性）可以证明是有用的，但是只有在测量设备的增益已知的情况下。
Single input, single output experiments can result in nonunique solutions for the rate constants of a linear compartmental model used to describe the pharmacokinetics. Where a finite number of solutions exists, a priori knowledge has to be used to distinguish between the solutions. Where there is an infinite number of solutions, assumptions have to be made about the values of some rate constants in order to obtain a unique solution for the others. Such experiments are considered and whether the addition of an extra input (simultaneously with the 1st input) or the taking of an extra measurement would result in a unique solution was determined. Perturbing a 2nd input apparently can be useful, but only if the perturbation is of different shape from the 1st input. Measurements of drug in urine and metabolite in plasma are generally not helpful in resolving identifiability of the drug dynamic model. If a radioactive tracer is used, the 2nd measurement (e.g., by externally scanning the radioactivity of the liver) can prove useful, but only if the gain of the measuring device is known.