Investigation on Effect of Drug Dosing Regiments on Drug Delivery in Solid Tumor via Lumped Parameter Modeling and Animal Experiments

This work aims to investigate the effects of dosing regiments on drug delivery in solid tumors and to validate them with experiments on rats. The lumped parameter models of pharmacokinetics and of drug delivery in tumor were developed to simulate time courses of average drug concentration (Ct) of tumor interstitium in two types of dosing regiments (i.e., single-shot and triple-shot ones). The two regiments were performed via antitumor drug, hydroxycamptothecin (HCPT), on rats, to measure the drug concentration in the tumor. The simulations of the drug concentration in the tumor of the two dosing regiments were conducted and compared with the experimental data on rats. The coefficients in the models were investigated. It is concluded that the triple-shot method is more effective than that of single-shot injection. The present lumped-parameter model is quantitatively competent for drug delivery in solid tumor.