Pharmacokinetic drug interactions can occur during any of the processes assumed to represent the fate of a drug in the body and contributing to the drug’s pharmacokinetic profile. The positive aspect is that for a new drug candidate, thorough preliminary studies can be undertaken before it appears on the market. This would confirm either the presence or absence of possible pharmacokinetic interactions that such a drug could cause. Such interactions may affect absorption of orally administered drugs, through different mechanisms such as: chemical interactions chelation and complication, alteration of gastrointestinal motility, changes in gastrointestinal pH, perturbation of gastrointestinal flora distribution drug metabolism especially through enzyme induction or inhibition effects, discussed separately in subchapter; and excretion Generally, as already outlined in, the process of absorption from the gastrointestinal tract in the case of orally administered drugs is variable and complex. Consequently, drug interactions of this type are difficult to predict.

However, the significant advances made in this area, especially during the last decade, permit (through mathematical approaches to prediction based on competitive enzyme inhibition) an early assessment of potential drug-drug interactions in patients that are taking concurrent medications. Most of these interactions refer to the rate of absorption, although, in some instances the extent of absorption may be affected as well. Changes in the rate of absorption – in most cases, delay of the process, can be of real clinical significance when referring either to drugs having a short half-life, or when achievement of rapid and high plasma levels may be critical (as may be the case with analgesics or hypnotics. Usually, this phenomenon is expected to appear if inappropriate combinations are administered without sufficient separation in time; therefore, most of these interactions can be avoided by simply allowing a two or three hour interval between the administration of the interacting drugs certain drugs given orally can sometimes react directly within the gastrointestinal tract, leading either to chelates or complexes, forms which are not readily absorbed.

Examples include interaction of tetracycline’s or fluoroquinolone antibiotics with metal ions (e.g. aluminum and magnesium in antacids, or iron salts), resulting in reduced drug absorption due to formation of a chelate complex within the gut; this chelation with divalent or trivalent ions, leading to insoluble complexes, may result in severely reduced plasma levels of the administered drugs and thus, therapeutic inefficacy. - interaction of digoxin, warfarin or thyroxine with cholestyramine and related anion exchange resins, with the same consequence of reduced absorption due to binding/complication in the gut (in fact, the adsorption of the former onto cholestyramine). Nevertheless, such effects may sometimes be used to therapeutic advantage: - activated charcoal, which acts as an adsorbent agent within the gut (although it can affect the absorption of certain drugs), may be used with good efficacy in the management of poisoning  cholestyramine and related anion exchange resins, binding cholesterol metabolites and bile acids, prevent their re-absorption in the intestinal lumen, thus lowering plasma levels of total cholesterol.

Best Regards,
Nancy Ella
Associate Managing Editor
Drug Designing: Open Access