Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, Hajduk Veljkova 3, 21000, Novi Sad, Republic of Serbia.
J Pharmacokinet Pharmacodyn. 2010 Apr;37(2):119-34. doi: 10.1007/s10928-009-9147-3. Epub 2010 Jan 14.
This study presents a new two compartmental model and its application to the evaluation of diclofenac pharmacokinetics in a small number of healthy adults, during a bioequivalence trial. In the model the integer order derivatives are replaced by derivatives of real order often called fractional order derivatives. Physically that means that a history (memory) of a biological process, realized as a transfer from one compartment to another one with the mass balance conservation, is taken into account. This kind of investigations in pharmacokinetics is founded by Dokoumetzidis and Macheras through the one compartmental models while our contribution is the analysis of multi-dimensional compartmental models with the applications of the two compartmental model in evaluation of diclofenac pharmacokinetics. Two experiments were preformed with 12 healthy volunteers with two slow release 100 mg diclofenac tablet formulations. The agreement of the values predicted by the proposed model with the values obtained through experiments is shown to be good. Thus, pharmacokinetics of slow release diclofenac can be described well by a specific two compartmental model with fractional derivatives of the same order. Parameters in the model are determined by the least-squares method and the Particle Swarm Optimization (PSO) numerical procedure is used. The results show that the fractional order two compartmental model for diclofenac is superior in comparison to the classical two compartmental model. Actually this is true in general case since the classical one is a special case of the fractional one.
本研究提出了一种新的双室模型及其在少数健康成年人中进行双氯芬酸药代动力学生物等效性试验的应用。在该模型中，整数阶导数被实数阶导数取代，通常称为分数阶导数。从物理意义上讲，这意味着考虑到生物过程的历史（记忆），即通过质量平衡守恒从一个隔室转移到另一个隔室的过程。这种药代动力学研究是由 Dokoumetzidis 和 Macheras 通过单室模型进行的，而我们的贡献是分析多维室模型，并将双室模型应用于双氯芬酸药代动力学的评价。对 12 名健康志愿者进行了两项实验，使用了两种 100mg 双氯芬酸缓释片制剂。结果表明，所提出的模型预测值与实验值吻合良好。因此，双氯芬酸的缓释药代动力学可以通过具有相同阶分数导数的特定双室模型很好地描述。模型中的参数通过最小二乘法确定，使用粒子群优化（PSO）数值程序。结果表明，与经典双室模型相比，双氯芬酸的分数阶双室模型具有优越性。实际上，在一般情况下，这是正确的，因为经典模型是分数模型的一个特例。
