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Gastrointestinal (GI) Physiology

Characteristics of GI physiology

pH Membrane Blood Supply Surface Area Transit Time By-pass liver
BUCCAL approx 6 thin Good, fast absorption with low dose small Short unless controlled yes
ESOPHAGUS 6 Very thick, no absorption - small short -
STOMACH 1 - 3
decomposition, weak acid unionized
normal good small 30 - 40 minutes, reduced absorption no
DUODENUM 5 - 7
bile duct, surfactant properties
normal good very large very short (6" long), window effect no
SMALL INTESTINE 6 -7 normal good very large 10 - 14 ft, 80 cm 2 /cm about 3 hours no
LARGE INTESTINE 6.8 - 7 - good not very large 4 - 5 ft long, up to 24 hr lower colon, rectum yes

Table 22.3.1 GI Physiology and Drug Absorption

Gastric emptying and motility

Figure 22.3.1 Dependence of Peak Acetaminophen Plasma Concentration as a Function of Stomach Emptying Half-life

Redrawn from Heading, R.C., Nimmo, J., Prescott, L.F. and Tothill, P. 1973.
The dependence of paracetamol absorption on the rate of gastric emptying,
Br. J. Pharmacol., 47, 415-421

Generally drugs are better absorbed in the small intestine (because of the larger surface area) than in the stomach, therefore quicker stomach emptying will increase drug absorption. For example, a good correlation has been found between stomach emptying time and peak plasma concentration for acetaminophen. The quicker the stomach emptying (shorter stomach emptying time) the higher the plasma concentration, Figure 22.3.1.

Also slower stomach emptying can cause increased degradation of drugs in the stomach's lower pH; e.g. l-dopa.

Volume of Ingested Material As volume increases initially an increase then a dcrease. Bulky material tends to empty more slowly than liquids
Type of Meal
Fatty food Decrease
Carbohydrate Decrease
Temperature of Food Increase in temperature, increase in empyting rate
Body Position Lying on the left side decreases emptying rate. Standing versus lying (delayed)
Drugs
Anticholinergics (e.g. atropine) Decrease
Narcotic (e.g. morphine) Decrease
Analgesic (e.g. aspirin) Decrease

Table 22.3.2 Factors Affecting Gastric Emptying

From Mayersohn, M. 1971.
Physiological Factors Influencing Drug Absorption,
Can. Pharm. J., 164-169

Effect of Food

Figure 22.3.2 Effect of Fasting versus Fed on Propranolol Concentrations

Melander, A., Danielson, K., Schersten, B. and Wahlin, E. 1977.
Enhancement of the bioavailability of propranolol and metaprolol by food,
Clin. Pharmacol. Ther., 22, 108-112

Food can effect the rate of gastric emptying. For example fatty food can slow gastric emptying and retard drug absorption. Generally the extent of absorption is not greatly reduced. Occasionally absorption may be improved. Griseofulvin absorption is improved by the presence of fatty food. Apparently the poorly soluble griseofulvin is dissolved in the fat and then more readily absorbed.

Propranolol plasma concentrations are larger after food than in fasted subjects. This may be an interaction with components of the food.

Other factors

Intestinal Motility and Transit Time (Mayersohn, 1971)

Food Retards transit


References

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Copyright 2001-3 David W. A. Bourne (david@boomer.org)


This file was last modified: Wednesday 26 May 2010 at 07:52 PM