EFFECTS OF NUTRITION ON DRUG METABOLISM
Pantuck and coworkers[197]
showed
that TPN could alter rates of hepatic drug oxidation in divergent ways, depending
on the type of nutrition furnished. After six healthy young male volunteers had
their total nutrition provided parenterally for 4 days with 5% dextrose followed
by an isocaloric amount of amino acids (Aminosyn, 3.5%) for 1 day, disposition of
the study drug antipyrine changed significantly. Compared with antipyrine clearance
values obtained on their home diet, the 4 days on dextrose significantly decreased
antipyrine clearance. In contrast, after only 1 day on parenteral amino acids, antipyrine
clearance increased markedly. Dextrose retarded, whereas amino acids enhanced, rates
of antipyrine elimination. This and other studies led Vesell and Biebuyck[198]
to suggest that anesthesiologists should consider that the doses of many drugs given
to surgical patients may need to be changed on commencement of TPN. Drugs eliminated
primarily by hepatic metabolism may especially require dosage adjustment.
These effects also occur from enteral feeding. In general, high-protein
diets significantly enhance drug clearance[199]
[200]
[201]
[202]
[203]
( Fig.
77-23
). Patients on a low-protein diet had delayed
Figure 77-23
A comparison of theophylline half-life results during
test diet periods. Bars represent means ±
SD. (Adapted from Feldman CH, Hutchinson VE, Pippenger CH, et al: Effect
of dietary protein and carbohydrate on theophylline metabolism in children. Pediatrics
66:956, 1980.)
drug clearance, regardless of the lipid-to-carbohydrate ratio of their diets. These
changes occurred without changes in volume of distribution or plasma protein binding.
The effect of protein is also seen in vegetarians; high-protein vegetarian diets
significantly enhance drug clearance.[204]
This
effect is so pronounced in experimental studies that variations in dietary protein
intake probably explain the otherwise inscrutable interpatient variation in response
to intravenously administered anesthetics. Starvation during a period of critical
illness retards clearance of many intravenous drugs. Enteral feedings directly inhibit
the absorption of enterally administered phenytoin; tube feedings must be discontinued
from 1 hour before to 1 hour after phenytoin dosing. The total volume of tube feedings
must compensate for the period of discontinuation.
