In vivo Passive and Iontophoretic Delivery of Lisinopril Using Wistar Rat Model

In-vivo studies using animal model were carried out to investigate the pharmacokinetic profile of passive and iontophoretically delivered lisinopril. Serum concentration versus time profiles from intravenous (IV), oral and iontophoretic routes were analyzed using non-compartmental analysis using TOPFIT ver. 2.0. Pharmacokinetic parameters such as AUC0–inf, terminal elimination rate constant (λz), clearance/F and Cmax, were calculated. To validate the calculations involved in non-compartmental analysis, the serum profiles were fitted using TOPFIT (ver. 2.0) software to the onecompartmental continuous infusion model with zero order absorption. The results of the IV bolus administration of lisinopril showed that the pharmacokinetics could be described by a two-compartment model. The bioavailability of passive and iontophoretically delivered lisinopril was 62.21 and 82.87 %, respectively which is significantly higher as compared to oral route (5.67 %). The corresponding values of Cmax were found to be 87, 95, 15.33 and 25.6 ng/ml, respectively for oral, IV bolus, passive and iontophoretically delivered lisinopril. The tmax for oral and IV route was 10 and 5 min, respectively, while it was 9.0 h both for passive and iontophoretic mediated transport of drug. The simple zero-order input rate and clearance effectively defined the delivery pattern of lisinopril from the iontophoretic patch. Good correlation was observed between the experimental data and data predicted by the model. Clearance estimated by the model is similar to the clearance calculated from intravenous administration, which supports the assumptions in the calculation of dose delivered by non-compartmental analysis.