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Effects of Food on Pharmacokinetics 1197

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Figure 69-1. Determinants of drug absorption, distribution, metabolism and excretion that may be modified by nutrient interactions. (Adapted
from Grahame-Smith DG, Aronson JK. In: The Oxford Textbook of Clinical Pharmacology and Drug Therapy. Oxford, UK: Oxford University
Press, 1985.) Rectal absorption in dogs and cats is subject to first-pass hepatic metabolism due to the small relative size of the rectum and
the lack of a hemorrhoidal plexus in these species. Transdermal could be substituted for rectal delivery (e.g., fentanyl patches in dogs and
cats). A good example of a drug absorbed across oral mucous membranes is buprenorphine in cats.

comitant consumption of food (Figure 69-1 and Tables 69-2 affected (Toothaker and Welling, 1980).
and 69-3).This interaction depends on the physical and chem- Alternatively, food does not affect absorption of other drugs
ical nature of the food and the drug, including such things as in people, including erythromycin estolate, oxazepam, propyl-
meal size and type,the formulation in which the drug is admin- thiouracil and enteric-coated aspirin granules in caplet form
istered, the order in which the food and drug are ingested and (Toothaker and Welling, 1980). In fact, food enhances the
the interval between their consumption (Roe, 1989). absorption of certain drugs (e.g., erythromycin ethylsuccinate,
Any food can reduce drug absorption by creating a barrier nitrofurantoin, hydrochlorothiazide and diazepam) (Toothaker
that prevents dispersion of the drug and dissolution of the and Welling, 1980). The rate and quantity of drug and nutrient
active agent in GI luminal contents. Drugs are better absorbed delivery are important, as evidenced by studies of hydralazine
in dilute vs. concentrated solution because of greater dissolution absorption. A bolus of nutrients impairs hydralazine uptake
and more rapid gastric emptying. In people, absorption of whereas a constant infusion over several hours does not (Semple
erythromycin stearate is reduced by approximately one-half et al, 1991). Total hydralazine absorption, however, is similar in
when taken with food or a small fluid volume, as compared both cases, although absorption is delayed by a bolus meal.
with a large fluid volume (Toothaker and Welling, 1980). Gastric emptying of drugs is delayed when they are admin-
Absorption of acetylsalicylic acid (aspirin), cephalexin, metro- istered with a meal. Gastric emptying of drugs is about 15 min-
nidazole, digoxin, hydralazine and cimetidine are similarly utes for fasted dogs, but may take up to three hours if given to