Pharmacokinetics/Pharmacodynamics

Drug-enteral-nutrition interactions: Some drugs potentially interact with enteral nutrition. The degree

of interaction and clinical significance varies.

Ciprofloxacin bioavailability is reduced when it is administered with enteral nutrition (with the

exception of the oral suspension), but most studies suggest that serum concentrations remain above

the minimum inhibitory concentration (MIC) for most bacterial pathogens.

Enteral nutrition has been reported to significantly reduce the absorption of levothyroxine,

phenytoin, and warfarin. One case report showed a reduction in voriconazole serum concentrations

when enteral nutrition was initiated (J Oncol Pharm Pract 2012;18:128-31).

A suggested solution to this interaction is to hold the enteral nutrition 1–2 hours before and after

drug administration. However, this poses two problems. First, interruption of enteral nutrition may

contribute to inadequate nutrition support. Second, this increases the difficulty of administering

the medications appropriately. Increasing the workload of nurses can lead to administration delays

or, even worse, errors. This is very important, because failure to withhold the enteral nutrition

could result in suboptimal dosing and effects of the interacting drug.

absorption. Examples from non-critically ill patients include increased gastric pH caused by histamine-2

receptor antagonists or proton pump inhibitors (can be used in the critically ill population for stress

ulcer prophylaxis), resulting in decreased absorption of ketoconazole, itraconazole, atazanavir,

indinavir, dasatinib, mycophenolate mofetil, cefpodoxime, and dipyridamole. Acid-suppressive drugs

increased nifedipine and digoxin absorption, and alendronate had a 2-fold increase in bioavailability in

the presence of these agents (Aliment Pharmacol Ther 2009;29:1219-29). Additionally, drug coating or

extended release matrices may be altered by pH changes and could potentially impact oral absorption.

For example, coadministration of a proton pump inhibitor with enteric coated ketoprofen altered the

maximum concentration and time to maximum concentration. Drug absorption depends on the drug’s

solubility and ability to permeate the intestinal mucosa. The distal end of the feeding tube can be in

the stomach, duodenum, or jejunum. Many drugs must be administered into the stomach or duodenum

so that they can be properly dissolved by gastric juices, bile, and pancreatic enzymes and can be fully

absorbed through the intestines. Thus, drugs like warfarin, which is absorbed high up in the small

bowel, and oral iron, which is dissolved in the stomach and absorbed in the duodenum, might not be

properly absorbed if they are administered via a jejunostomy tube.

The overall uncertainty of a patient’s ability to absorb drugs from the GI tract often results in the clinician’s

avoidance of enterally administered drugs because they want to ensure adequate bioavailability. The

decision to use the GI route of administration is arbitrary, and in some cases this approach may be more

costly. Many clinicians anecdotally use tolerance of enteral feedings as a surrogate marker for normal

drug absorption. The definition of tolerance is debatable and assessment of tolerance is highly variable,

so it is not an ideal maker for drug absorption. If a drug known to interact with enteral nutrition requires

enteral administration, nutrition should be interrupted for the minimum duration possible around drug

administration.

clinical practice has not abandoned these routes of administration. Some clinicians advocate using larger

doses of drugs being administered subcutaneously, but no studies have verified the safety or efficacy

of this practice. Small studies investigating enoxaparin dosing in medically ill and trauma patients

with obesity found improved anti-Xa serum concentrations when using a weight-based dosing method

(0.5 mg/kg every 12 hours) compared with standard dosing. This suggests that larger subcutaneous fat

distribution can alter the pharmacokinetics and PD of some medications (Thromb Res 2010;125:220-3;