Physiological Pharmaceutics

Small intestine 133colonic absorption since, in the absence of absorption from the proximal colon, only amaximum of 3–5 hours is available for absorption from the small intestine in the fastingstate. Absorption from the proximal colon affords a further six hours of contact time. Thismodel would predict a marked increase in bioavailability for formulations of poorlyabsorbed drugs such as frusemide taken with a heavy meal since the meal provides a slowinput into the upper small intestine, the major site of absorption (Figure 6.14).Interaction with foodThe presence of food may influence the absorption of drugs and can either enhance, delayor reduce absorption 77 . The most serious problem with such studies is that variations in drugabsorption may be due to several different effects. Primarily, the effect of food on gastricemptying is considerable, and variations in the rate at which food is presented to the smallintestine will change the drug pharmacokinetics. Secondly, the drug can interact with thefood in the intestinal lumen, adsorb to food or be or absorbed by it. Metal ions present infood such as milk can chelate drug, or the drug can bind to dietary proteins thus changingits bioavailability. The presence of viscous chyme can act as a physical barrier reducing drugaccess to the absorbing surface. Finally, food may influence the absorption process by directinterference with the epithelial biochemistry; for example the absorption of a drug that wastaken up actively by a carbohydrate transport system would be slowed in the presence ofa large carbohydrate meal which would compete for the transporter. In practise it isextremely difficult to disentangle these factors and so most studies simply report an overalleffect.The absorption of drugs such as penicillin V and G, theophylline and erythromycinis reduced by the presence of food, but food delays the absorption of other drugs(cimetidine, metronidazole and digoxin). The effect of food on drug absorption can bedependent on the type of dosage form used, the excipients and the form of the drug, forexample erythromycin stearate in film coated tablets demonstrated reduced absorption withfood, erythromycin estolate in suspension was unaffected by food, but absorption oferythromycin ethylsuccinate in suspension and erythromycin estolate in capsules wasincreased by the presence of food 77 . A co-administered meal decreases the oral absorptionof bidisomide and does not influence the oral absorption of the chemically-relatedFigure 6.14 Absorption profile for a drug which is poorly absorbed from the colon whenadministered in a zero-order sustained release dosage form