PHARMACOLOGY AND THERAPEUTICS-PREDICTION OF A DRUG INTERACTIONS
All drugs used in therapeutic interventions have a potential to cause either a drug-drug, or drug-food interaction. Such effects, will depends on both patient- and drug-specific factors. Patient factors can include intrinsic drug clearance, genetics, gender, concurrent diseases, and diet. Drug-specific factors include dose, route of administration, drug formulation, and the sequence of drug administration. Pharmacokinetic Mechanisms: The gastrointestinal absorption of drugs may be affected by concurrent use of other agents that have the following specificities;
(1) Have a large surface area upon which the drug can be adsorbed,
(2) Bind or chelate,
(3) Alter gastric pH,
(4) Alter gastrointestinal motility, or
(5) Affect transport proteins such as P-glycoprotein and organic anion transporters. One must distinguish between effects on absorption rate and effects on extent of absorption.
A reduction in only the absorption rate of a drug is seldom clinically important, whereas a reduction in the extent of absorption is clinically important if it results in sub therapeutic serum concentrations.
The mechanisms by which drug interactions alter drug distribution include;
(1) Competition for plasma protein binding,
(2) Displacement from tissue binding sites, and
(3) Alterations in local tissue barriers, eg, P-glycoprotein inhibition in the blood brain barrier. Although competition for plasma protein binding can increase the free concentration (and thus the effect) of the displaced drug in plasma, the increase will be transient owing to a compensatory increase in drug disposition. The clinical importance of protein binding displacement has been overemphasized; current evidence suggests that such interactions are unlikely to result in adverse effects. Displacement from tissue binding sites would tend to transiently increase the blood concentration of the displaced drug.
