Kinetic analysis of demethylation of 13C-aminopyrine in healthy dogs

Objective - To describe the kinetics of demethylation of ¹³C-aminopyrine in healthy dogs for use in determining the most appropriate time for collection of blood samples for a ¹³C-aminopyrine demethylation blood test for evaluation of hepatic function. Animals - 9 healthy dogs. Procedures - A 2-mL baseline blood sample was collected into an evacuated heparinized tube, and ¹³C-aminopyrine was administered to each dog (2 mg/kg, IV). Additional 2-mL blood samples were collected 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 180, 240, 300, and 360 minutes after ¹³C-aminopyrine administration. The CO₂ was extracted from blood samples by addition of a strong acid, and the percentage dose of ¹³CO₂ (PCD in the extracted gas was determined by fractional mass spectrometry. Results - No dogs had gross evidence of adverse effects, and all had an increase in PCD after IV administration of ¹³C-aminopyrine. The PCD had the least variability among 5 variables used to evaluate hepatic clemethylating capacity. Peak PCD was detected at 30 minutes in 1 dog, 45 minutes in 5 dogs, 60 minutes in 2 dogs, and 75 minutes in 1 dog. The mean PCD for the 9 dogs peaked at 45 minutes after ¹³C-aminopyrine administration. Conclusions and Clinical Relevance - PCD appears to be the preferable variable for evaluation of hepatic demethylating capacity. Intravenous administration of ¹³C-aminopyrine leads to a consistent increase in PCD. Mean PCD peaked 45 minutes after administration, suggesting that blood sample collection 45 minutes after ¹³C-aminopyrine administration may be appropriate for use in estimating hepatic demethylating capacity.