Pharmacokinetic modulation of substrate drugs via the inhibition of drug-metabolizing enzymes and transporters using pharmaceutical excipients

Background Pharmaceutical excipients are used for formulating drugs to suit their intended use and effect. These excipients influence drug solubility, manufacturability, and ability to control drug release in vitro and in vivo. They also affect intestinal permeability and metabolism by modulating drug-metabolizing enzymes and transporters.Area covered We have reviewed the effect of pharmaceutical excipients on cytochrome P450s (CYPs)-and uridine-5 '- diphospho-glucuronosyltransferases (UGTs)-mediated metabolic activities, and solute carrier transporters-and efflux transporters-mediated transport activities. We also reviewed the formulation strategies and pharmaceutical excipients that modulate drug metabolism and permeability to increase oral bioavailability (BA) by facilitating the required drug pharmacokinetics.Expert opinion The solubilization, permeation enhancement, and pharmacokinetic modulation with functional excipients are crucial for developing formulations ranging from intravenous to oral and enhancing the oral BA. Therefore, the selection of pharmaceutical excipients to formulate drugs with low solubility and permeability should be based on their safety, solubilizing capacity, interactions with intestinal metabolism, transport processes, and formulation stability.