Page 1154 - Small Animal Clinical Nutrition 5th Edition

1202 Small Animal Clinical Nutrition

the development of fasting hyperbilirubinemia.
Dietary protein-related changes in renal blood flow and renal
VetBooks.ir tubular transport can simultaneously affect the clearance of
drugs eliminated in urine (Park et al, 1989). Increased dietary
protein intake in dogs (from 9.4 to 27.3% on a dry matter basis)
increases the elimination of gentamicin and reduces the poten-
tial for nephrotoxicity, presumably by stimulating renal blood
flow (Behrend et al, 1994; Grauer et al, 1994). In people, low-
protein diets (19 vs. 268 g/day) decrease the hepatic metabo-
lism of allopurinol to oxypurinol, and decrease renal excretion
of oxypurinol (Berlinger et al, 1985). The pharmacokinetics of
allopurinol and oxypurinol in dogs do not appear to be affect-
ed by dietary protein (Bartges et al, 1997).
One canine study determined the effects of various foods
on the pharmacokinetics of phenobarbital and the interactive
effects of changes in body composition and metabolic rate
(Maguire et al, 2000). Phenobarbital pharmacokinetic stud-
ies were performed in 27 healthy, adult, sexually intact female
beagles before and two months after they were fed one of
three commercially available foods: 1) a maintenance food, 2)
Figure 69-4. The hepatic phase II biotransformation system for a low-protein veterinary therapeutic food for renal failure
drug metabolism. (Adapted from Fettman MJ, Butler RN, McMich- patients or 3) a low-fat veterinary therapeutic food for weight
ael AJ, et al. Metabolic phenotypes and colorectal neoplasia. loss. Phenobarbital, 3 mg/kg body weight orally, twice daily
Journal of Gastroenterology and Hepatology 1991; 6: 81-90.) was administered to all three groups. Volume of distribution,
Key: P-450 = cytochrome P-450, GSH = reduced glutathione, GST mean residence time and half-life (t ) decreased significant-
1/2
= glutathione-S-transferase, acetyl-CoA = acetyl-coenzyme A, NAT ly, whereas clearance rate and elimination rate increased sig-
= N-acetyltransferase, UDPGA = uridine diphosphoglucuronic acid,
nificantly with time in all groups. Dietary protein or fat
UDP-GT = UDP-glucuronyl transferase, SAM = adenosylmethion-
restriction induced significantly greater changes: t (hours)
ine, S-MT = S-methyltransferase. 1/2
was lower in dogs fed the renal food (25.9 ± 6.1) and the
changes in the macronutrient composition of the diet can sig- weight-loss food (24.0 ± 4.7) compared to results from dogs
nificantly alter hepatic drug metabolism. fed the maintenance food (32.9 ± 5.2). Phenobarbital clear-
ance rate (ml/kg/min.) was significantly higher in dogs fed
Dietary Protein Intake the weight-loss food (0.22 ± 0.05) compared to clearance
In experimental studies in rats, low dietary protein intake rates in dogs fed the maintenance food (0.17 ± 0.03) or the
reduced the metabolism and increased the toxicity of pentobar- renal food (0.18 ± 0.03). Induction of serum alkaline phos-
bital, strychnine and zoxazolamine (Guengerich, 1984). The phatase activity (IU/l) was greater in dogs fed the renal food
activities of the mixed-function oxidase enzymes flavoprotein (192.4 ± 47.5) and the weight-loss food (202.0 ± 98.2) than
reductase and cytochrome b5 are decreased by dietary protein in dogs fed the maintenance food (125.0 ± 47.5).The authors
restriction. Inducibility of cytochrome P-450 by phenobarbital concluded that phenobarbital dosage should be reevaluated if
in rats is also decreased by feeding less dietary protein (Guen- a dog’s diet, body weight or body composition changes dur-
gerich, 1995). ing treatment. Veterinarians in clinical practice, researchers
High-protein (e.g., 44 vs. 10% of kcal, as fed), low-carbohy- evaluating drug pharmacokinetics (phenobarbital and other
drate foods (e.g., 35 vs. 70% of kcal, as fed) enhance the hepat- drugs) and pet food companies that market veterinary thera-
ic metabolism and excretion of many different drugs in people, peutic foods with nutrient profiles that differ from typical
including acetaminophen, oxazepam, theophylline, proprano- commercial maintenance foods should be aware that a die-
lol and estradiol (Guengerich, 1995; Fagan et al, 1987; Pan- tary change may markedly affect the pharmacokinetics of
tuck et al, 1991). Conversely, consumption of protein-restrict- concurrent drug therapy.
ed foods for as few as 10 days significantly decreases elimina-
tion of these drugs. Dietary Carbohydrate Intake
Certain essential amino acids may stimulate hepatic protein High carbohydrate intake (70 vs. 35% on a dry matter basis) in
synthesis and thereby induce the hepatic mixed-function oxi- people depresses oxidative drug metabolism (Fagan et al, 1987).
dase system. Sulfur-containing amino acids can promote hepat- High dietary fructose, glucose and sucrose levels increase barbi-
ic drug metabolism by increasing glutathione synthesis and sub- turate sleeping time and decrease in vitro metabolism of barbi-
sequent conjugation reactions (Fettman, 1991). Starvation can turates in mice (Guengerich, 1995). Parenteral glucose has the
reduce the activity of glutathione-S-transferase and the synthe- same effect in dogs and cats; thus, high dietary intake of these
sis of glutathione for conjugation; events that also participate in carbohydrates may likely modify barbiturate responses in these