Rutin and Physalis peruviana Extract: Population Pharmacokinetics in New Zealand Rabbits

Background/Objectives: An extract of calyces from Physalis peruviana with hypoglycemic activity is being considered as a potential herbal medicine. Preclinical pharmacokinetics (PK) studies of the extract in rats, focusing on plasma concentrations of its main compound, rutin, and its metabolites, revealed PK interactions in the extract matrix that improved the absorption of rutin metabolites compared to the pure compound, among other PK effects. This research aimed to study the PK of rutin alone and in the extract and assess potential PK interactions in the extract matrix on the flavonoid and its metabolites in rabbits, a nonrodent species; Methods: Animals received pure rutin or extract orally and intravenously. The PK analysis used noncompartmental and population pharmacokinetics (popPK) methods, and simple allometry was applied to predict human PK parameters; Results: The rutin concentration-time profile fit a two-compartment model with first-order elimination, while its metabolites fit a double first-order absorption model. The extract matrix led to increased absorption, distribution, and elimination of rutin as well as increased bioavailability of its metabolites in rabbits; Conclusions: The popPK model defined the equations for PK parameters describing these findings, and the increased volume of distribution and clearance of rutin was maintained in human predictions. These results will support the development of a new herbal medicine.