Maguire PJ, Fettman MJ, Smith MO, Greco DS, Turner AS et al
Effects of diet on pharmacokinetics of phenobarbital in healthy dogs.

J Am Vet Med Assoc, 217(6): 847-852, 2000
ISSN: 0003-1488 Journal of the American Veterinary Medical Association (PubMed)

Abstract
Objective - To determine effects of various diets on the pharmacokinetics of phenobarbital and the interactive effects of changes in body composition and metabolic rate. Design - Prospective study. Animals - 27 healthy sexually intact adult female Beagles. Procedure - Pharmacokinetic studies of phenobarbital were performed before and 2 months after dogs were fed 1 of 3 diets (group 1, maintenance diet; group 2, protein-restricted diet; group 3, fat- and protein-restricted diet) and treated with phenobarbital (approx 3 mg/kg [1.4 mg/lb] of body weight, PO, q 12 h). Pharmacokinetic studies involved administering phenobarbital (15 mg/kg [6.8 mg/lb], IV) and collecting blood samples at specific intervals for 240 hours. Effects of diet and time were determined by repeated-measures ANOVA. Results - Volume of distribution, mean residence time, and half-life (t( [half] )) of phenobarbital significantly decreased, whereas clearance rate and elimination rate significantly increased with time in all groups. Dietary protein or fat restriction induced significantly greater changes: t( [half] ) (hours) was lower in groups 2 (mean +/- SD; 25.9 +/- 6.10 hours) and 3 (24.0 +/- 4.70) than in group 1 (32.9 +/- 5.20). Phenobarbital clearance rate (ml/kg/min) was significantly higher in group 3 (0.22 +/- 0.05 ml/kg/min) than in groups 1 (0.17 +/- 0.03) or 2 (0.18 +/- 0.03). Induction of serum alkaline phosphatase activity (U/L) was greater in groups 2 (192.4 +/- 47.5 U/L) and 3 (202.0 +/- 98.2) than in group 1 (125.0 +/- 47.5). Conclusions and Clinical Relevance - Clinically important differences between diet groups were observed regarding pharmacokinetics of phenobarbital, changes in CBC and serum biochemical variables, and body composition. Drug dosage must be reevaluated if a dog's diet, body weight, or body composition changes during treatment. Changes in blood variables that may indicate liver toxicosis caused by phenobarbital may be amplified by diet-drug interactions.