Pharmacokinetics and Alterations in Glucose and Insulin Levels After a Single Dose of Canagliflozin in Healthy Icelandic Horses
Peter Michanek, Johan Bröjer, Inger Lilliehöök, Cathrine T. Fjordbakk, Minerva Löwgren, Mikael Hedeland, Jonas Bergquist, Carl Ekstrand
Abstract
ABSTRACT Canagliflozin (CFZ) is a sodium‐glucose cotransporter‐2 inhibitor that has shown promising results as a drug for the treatment of insulin dysregulation in horses. Even though CFZ is used clinically, no pharmacokinetic data has previously been published. In this study, the pharmacokinetics of CFZ after administration of a single oral dose of 1.8 mg/kg in eight healthy Icelandic horses was examined. Additionally, the effect of treatment on glucose and insulin levels in response to a graded glucose infusion was investigated. Plasma samples for CFZ quantification were taken at 0, 0.33, 0.66, 1, 1.33, 1.66, 2, 2.33, 2.66, 3, 3.5, 4, 5, 6, 8, 12, 24, 32, and 48 h post administration. CFZ was quantified using UHPLC coupled to tandem quadrupole mass spectrometry (UHPLC‐MS/MS). A non‐compartmental analysis revealed key pharmacokinetic parameters, including a median T max of 7 h, a C max of 2350 ng/mL, and a t 1/2Z of 28.5 h. CFZ treatment reduced glucose (AUC GLU , p = 0.001) and insulin (AUC INS , p = 0.04) response to a graded glucose infusion administered 5 h after treatment. This indicates a rapid onset of action following a single dose in healthy Icelandic horses. No obvious adverse effects related to the treatment were observed.