Effects of diet on pharmacokinetics of phenobarbital in healthy dogs.
OBJECTIVE
To determine effects of various diets on the pharmacokinetics of phenobarbital and the interactive effects of changes in body composition and metabolic rate.


METHODS
Prospective study.


METHODS
27 healthy sexually intact adult female Beagles.


METHODS
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, p.o., q 12 h). Pharmacokinetic studies involved administering phenobarbital (15 mg/kg [6.8 mg/lb], i.v.) 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 (t1/2) 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: t1/2 (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
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.
Maguire
P J
PJ
Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins 80523, USA.
Fettman
M J
MJ
Smith
M O
MO
Greco
D S
DS
Turner
A S
AS
Walton
J A
JA
Ogilvie
G K
GK
D000469:Alkaline Phosphatase / Q000097:blood; D000821:Animal Feed; D000818:Animals; D000927:Anticonvulsants / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002153:Calorimetry, Indirect / Q000662:veterinary; D002784:Cholesterol / Q000097:blood; D018752:Diet, Fat-Restricted / Q000662:veterinary; D018753:Diet, Protein-Restricted / Q000662:veterinary; D004285:Dogs / Q000502:physiology*; D004906:Erythrocyte Count / Q000662:veterinary; D005260:Female; D005454:Fluorescence Polarization / Q000662:veterinary; D018565:Food-Drug Interactions; D006207:Half-Life; D006400:Hematocrit / Q000662:veterinary; D006454:Hemoglobins / Q000032:analysis; D010634:Phenobarbital / Q000097:blood / Q000493:pharmacokinetics*; D011446:Prospective Studies; D011897:Random Allocation; D012640:Seizures / Q000517:prevention & control / Q000662:veterinary; D012709:Serum Albumin / Q000032:analysis
D000927:Anticonvulsants; D006454:Hemoglobins; D012709:Serum Albumin; D002784:Cholesterol; D000469:Alkaline Phosphatase; D010634:Phenobarbital