Abstract
OBJECTIVE To investigate the pharmacokinetics of metformin hydrochloride in healthy dogs after IV and oral bolus administrations and determine the oral dose of metformin that yields serum concentrations equivalent to those thought to be effective in humans. ANIMALS 7 healthy adult mixed-breed dogs. PROCEDURES Each dog was given a single dose of metformin IV (mean ± SD dose, 24.77 ± 0.60 mg/kg) or PO (mean dose, 19.14 ± 2.78 mg/kg) with a 1-week washout period between treatments. For each treatment, blood samples were collected before and at intervals up to 72 hours after metformin administration. Seventy-two hours after the crossover study, each dog was administered metformin (mean dose, 13.57 ± 0.55 mg/kg), PO, twice daily for 7 days. Blood samples were taken before treatment initiation on day 0 and immediately before the morning drug administration on days 2, 4, 6, and 7. Serum metformin concentrations were determined by means of a validated flow injection analysis-tandem mass spectrometry method. RESULTS After IV or oral administration to the 7 dogs, there was high interindividual variability in mean serum metformin concentrations over time. Mean ± SD half-life of metformin following IV administration was 20.4 ± 4.1 hours. The mean time to maximum serum concentration was 2.5 ± 0.4 hours. Mean systemic clearance and volume of distribution were 24.1 ± 7.8 mL/min/kg and 44.8 ± 23.5 L/kg, respectively. The mean oral bioavailability was 31%. CONCLUSIONS AND CLINICAL RELEVANCE The study data indicated that the general disposition pattern and bioavailability of metformin in dogs are similar to those reported for cats and humans.
Highlights
From the Department of Small Animal Clinical Sciences, Western College of Veterinary Medicine (Johnston, MacDonald Dickinson, Gaunt), and the College of Pharmacy and Nutrition (Alcorn), University of Saskatchewan, Saskatoon, SK S7N 2Z4, Canada
RELEVANCE The study data indicated that the general disposition pattern and bioavailability of metformin in dogs are similar to those reported for cats and humans. (Am J Vet Res 2017;78:1193–1199)
Metformin (1,1-dimethylbiguanide) is a biguanide primarily used for the management of non–insulin-dependent diabetes mellitus in humans and is the recommended first-line treatment following diagnosis.[1]
Summary
Metformin hydrochloridea (500 mg) was dissolved in 10 mL of saline (0.9% NaCl) solution and passed through a filter (pore diameter, 0.2 μm) for IV administration. Metformin hydrochloride tabletsb (500 mg each) were used. Seven healthy adult mixed-breed dogs (2 sexually intact males, 2 neutered males, 1 sexually intact female, and 2 spayed females) between 2 and 3 years old and weighing between 25.7 and 29.2 kg (mean ± SD weight, 27.96 ± 1.21 kg) were used. All dogs were considered healthy at the time of the study. The dogs had been well adapted to their environment and were accustomed to being handled. They were housed at the Western College of Veterinary Medicine Animal Care Unit. The study had 2 phases, was approved by the University of Saskatchewan’s Animal Research Ethics Board, and adhered to the Canadian Council on Animal Care guidelines for humane animal use
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
