Compartmental analysis of ranitidine doubled peak plasma profile after oral administration to health volunteers

Abstract

The aim of this study was to describe the double peak plasma pharmacokinetic profile of ranitidine after oral administration to healthy volunteers using non-compartmental and compartmental analysis. A single 300 mg dose of ranitidine was given to ten healthy volunteers (5 male and 5 female). Blood samples were drawn at different times and analyzed by HPLC. Plasma profiles were evaluated by non-compartmental and compartmental approaches. The non-compartmental parameters determined were k (0.0054 ± 0.0010 min-1), t1/2 (2.2 ± 0.4 h), Vdss/F (265.3 ± 70.6 L), Cl/F (84.8 ± 24.3 L/h) and AUC (225916 ± 54099 ng*min/mL). The compartmental analysis was carried out using a two compartments body model, with first order absorption from two different sites. The parameters determined were k21 (0.0149 ± 0.0133 min-1), ka1 (0.0117 ± 0.0073 min-1), ka2 (0.1496 ± 0.1699 min-1), Vc (128 ± 75.2 L), a (0.0299 ± 0.0319 min-1), b (0.0074 ± 0.0014 min-1) and time for the beginning of the absorption from the second site (126.7 ± 58.1 min). The model used in the compartmental analysis was adequate to describe the double peak of ranitidine plasma profile and to determine the pharmacokinetic parameters.