Factors of Drug Absorption

Clinical Factors:-

1) Diseases

  • Parkinson's disease may have difficulty swallowing and greatly diminished gastrointestinal motility. A case was reported in which the patient could not be controlled with regular oral levodopa medication because of poor absorption. Infusion of oral levodopa solution using a jtube gave adequate control of his symptom.

Patients on tricyclic antidepressants (imiprimine, amitriptyline, and nortriptyline) and antipsychotic drugs (phenothiazines) with anticholinergic side effects may have reduced gastrointestinal motility or even intestinal obstructions. Delays in drug absorption, especially with slow-release products, have occurred.

  • Achlorhydricpatients may not have adequate production of acids in the stomach; stomach HCl is essential for solubilizing insoluble free bases. Many weak-base drugs that cannot form soluble salts will remain undissolved in the stomach when there is no hydrochloric acid present and are therefore unabsorbed. Salt forms of these drugs cannot be prepared because the free base readily precipitates out due to the weak basicity.

Dapsone, itraconazole, and ketoconazole may also be less well absorbed in the presence of achlorhydria. In patients with acid reflux disorders, proton pump inhibitors, such as omeprazole, render the stomach achlorhydric, which may also affect drug absorption. Coadministering orange juice, colas, or other acidic beverages can facilitate the absorption of some medications requiring an acidic environment.

  • HIV-AIDSpatients are prone to a number of gastrointestinal (GI) disturbances, such as increased gastric transit time, diarrhea, and achlorhydria. Rapid gastric transit time and diarrhea can alter the absorption of orally administered drugs. Achlorhydria may or may not decrease absorption, depending on the acidity needed for absorption of a specific drug. Indinavir, for example, requires a normal acidic environment for absorption. The therapeutic window of indinavir is extremely narrow, so optimal serum concentrations are critical for this drug to be efficacious.

  • Congestive heart failure (CHF) patients with persistent edema have reduced splanchnic blood flow and develop edema in the bowel wall. In addition, intestinal motility is slowed. The reduced blood flow to the intestine and reduced intestinal motility results in a decrease in drug absorption. For example, furosemide (Lasix), a commonly used loop diuretic, has erratic and reduced oral absorption in patients with CHF and a delay in the onset of action.

  • Crohn's disease is an inflammatory disease of the distal small intestine and colon. The disease is accompanied by regions of thickening of the bowel wall, overgrowth of anaerobic bacteria, and sometimes obstruction and deterioration of the bowel. The effect on drug absorption is unpredictable, although impaired absorption may potentially occur because of reduced surface area and thicker gut wall for diffusion.

2) Drugs

  • Anticholinergic drugs in general may reduce stomach acid secretion. Propantheline bromide is an anticholinergic drug that may slow stomach emptying and motility of the small intestine. Tricyclic antidepressants and phenothiazines also have anticholinergic side effects that may cause slower peristalsis in the GI tract. Slower stomach emptying may cause delay in drug absorption.

  • Metoclopramide is a drug that stimulates stomach contraction, relaxes the pyloric sphincter, and, in general, increases intestinal peristalsis, which may reduce the effective time for the absorption of some drugs and thereby reduce the peak drug concentration and the time to reach peak drug concentration. For example, digoxin absorption from a tablet is reduced by metoclopramide but increased by an anticholinergic drug, such as propantheline bromide. Allowing more time in the stomach for the tablet to dissolve generally helps with the dissolution and absorption of a poorly soluble drug, but would not be helpful for a drug that is not soluble in stomach acid.

  • Antacids should not be given with cimetidine, because antacids may reduce drug absorption. Antacids containing aluminum, calcium, or magnesium may complex with drugs such as tetracycline, ciprofloxacin, and indinavir, resulting in a decrease in drug absorption. To avoid this interaction, antacids should be taken 2 hours before or 6 hours after drug administration. As mentioned, proton pump inhibitors, such as omeprazole, render the stomach achlorhydric, which may also affect drug absorption.

  • Cholestyramine is a nonabsorbable ion-exchange resin for the treatment of hyperlipemia. Cholestyramine adsorbs warfarin, thyroxine, and loperamide, similar to activated charcoal, thereby reducing absorption of these drugs.

  • Absorption of calcium in the duodenum is an active process facilitated by vitamin D, with calcium absorption as much as four times more than that in vitamin D deficiency states. It is believed that a calcium-binding protein, which increases after vitamin D administration, binds calcium in the intestinal cell and transfers it out of the base of the cell to the blood circulation.

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