Beneficial pharmacokinetic drug interactions: a tool to improve the bioavailability of poorly permeable drugs

Abstract

Simultaneous oral intake of herbs, supplements, foods and drugs with other drug(s) may result in pharmacokinetic or pharmacodynamic interactions with the latter. Although these interactions are often associated with unwanted effects such as adverse events or inefficacy, they can also produce effects that are potentially beneficial to the patient. Beneficial pharmacokinetic interactions include the improvement of the bioavailability of a drug (i.e., by enhancing absorption and/or inhibiting metabolism) or prolongation of a drug’s plasma level within its therapeutic window (i.e., by decreasing excretion), whereas beneficial pharmacodynamic interactions include additive or synergistic effects. Mechanisms by which pharmacokinetic interactions can cause beneficial effects include enhancement of membrane permeation (e.g., structural changes in the epithelial cell membranes or opening of tight junctions), modulation of carrier proteins (e.g., inhibition of efflux transporters and stimulation of uptake transporters) and inhibition of metabolic enzymes. In the current review, selected pharmacokinetic interactions between drugs and various compounds from different sources including food, herb, dietary supplements and selected drugs are discussed. These interactions may be exploited in the future to the benefit of the patient, for example, by delivering drugs that are poorly bioavailable in therapeutic levels via alternative routes of administration than parenteral injection