Influence of food and diet on gastrointestinal drug absorption: A review

1 The present study was designed to investigate the effect of food and of a raised intragastric pH on the bioavailability of two prodrug P-lactam, antibiotics, namely bacampicillin and cefuroxime axetil. 2 Six healthy volunteers participated in an intraindividual comparison of absorption of (a) prodrug, (b) breakfast, followed by prodrug, (c) breakfast, ranitidine and sodium bicarbonate followed by prodrug, and (d) ranitidine and sodium bicarbonate, followed by prodrug. All volunteers were dosed with both bacampicillin and cefuroxime axetil under the above regimens. The drug-free periods between trials were 7 days. 3 Blood samples were obtained before and 20, 40, 60, 90, 120, 150, 180, 210 min and 4, 5, 6, 8 and 10 h after administration. The urine was collected for a period of 10 h after dosing with the antibiotic. An estimation of the relative bioavailability of the drugs under the various regimens was made by comparing the average areas under the serum concentration time curves and also the amounts recovered in the urine.4 Both food and reduced gastric acidity decreased the bioavailability of bacampicillin (as ampicillin) and these variables had an additive lowering effect on the AUC and percentage urinary recovery. Possibly this ester becomes partially hydrolyzed prior to absorption on raising the intragastric pH. Adsorption onto food components or complexing with proteins may also play a role in the reduced bioavailability of bacampicillin in the presence of food. 5 In contrast, the absorption of the cefuroxime ester was enhanced postprandially. This may be rationalized in terms of delayed gastric emptying and gastrointestinal transit which allows more complete dissolution or prolonged residence at the most favourable site of absorption in the intestine. However, the raising of the intragastric pH by the concomittant administration of ranitidine and sodium bicarbonate, reduced the enhanced postprandial absorption. Possibly the good absorption of cefuroxime axetil requires a sufficient low gastric pH to allow the drug to dissolve in the gastric juices.

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Influence of food and reduced gastric acidity on the bioavailability of bacampicillin and cefuroxime axetil.

Sommers¹,

Wyk²,

Moncrieff³

et al. 1984

“…The decreased absorption rate seen after food intake was most likely due to delayed gastric emptying. Delayed gastric emptying, in turn, has been shown to be caused by hot meals, solutions of high viscosity, fat and-to a lesser extent-by proteins and carbohydrates (Welling, 1977).…”

Section: Discussionmentioning

confidence: 99%

Food intake increases the relative oral bioavailability of vanoxerine.

Ingwersen

Mant

Larsen

1993

Each of 12 healthy male subjects received single oral doses of 100 mg vanoxerine (GBR 12909), a dopamine reuptake inhibitor with potential antidepressant activity, on three different occasions (fasting, after a low‐fat meal and after a high‐fat meal) according to a randomized, cross‐over design. The mean tmax value increased from 0.82 h after fasting to 1.44 h after a low‐fat meal and to 2.46 h after a high‐fat meal. Only modest food effects were seen on mean Cmax values (55 nM, 52 nM and 84 nM, after fasting, after the low‐fat meal and after the high‐ fat meal, respectively) but values of AUC up to the last measurable concentration (AUC(0,t)) increased by 76% (from 110 to 194 nM h) after the low‐fat meal and by 255% (from 110 to 391 nM h) after the high‐fat meal compared with fasting. All of these effects were statistically significant except for the differences in tmax and Cmax between fasting and the low‐fat meal. The mechanism of these changes is unclear, but it seems likely that food may lower the first‐pass metabolism of vanoxerine, as has been shown for other lipophilic basic drugs.

“…In most cases, food is associated with delayed or decreased drug absorption (Welling, 1977), although numerous examples of unaffected or increased absorption have also been shown (Welling, 1977;Colburn et al, 1983;Melander, 1978). The effect of food on the bioavailability of different angiotensin-converting enzyme (ACE) inhibitors has also been studied.…”

Section: Introductionmentioning

confidence: 99%

The influence of food on the pharmacokinetics and ACE inhibition of cilazapril.

Massarella

Defeo

Brown

et al. 1989

1 The influence of food on the pharmacokinetics and angiotensin-converting enzyme (ACE) inhibitory effects of oral 5 mg doses of cilazapril was investigated in a two-way crossover study in 16 volunteers. 2 Plasma and urine concentrations of cilazaprilat, the active diacid metabolite of cilazapril, and plasma ACE activity were determined by a radio-enzymatic method.3 Cmax decreased by 30% (P < 0.05) with a delay in tmax of 1 h (P < 0.05) and area under curve (AUC) was decreased by 14% (P < 0.05). The elimination rate was unaltered.4 Onset of ACE inhibition was delayed by 30 min but degree and duration were unaffected.5 The effect of food on the bioavailability of cilazapril at this dose would not be expected to be clinically significant.