A REVIEW ON BENEFICIAL PHARMACOKINETIC INTERACTIONS IN ENHANCING BIOAVAILABILITY OF POORLY PERMEABLE DRUGS

Dr. Botta Gayathri*, Dr. S. Niveditha, K. Hetrina Ruth, V. Jokesh, Ch. Varshitha, N. Reddy Yamini and Sk. Anisa

Pharmacokinetic interactions between drugs and other co-administered substances—such as additional drugs or food components—can significantly influence drug absorption, distribution, metabolism, and excretion (ADME). While often viewed as a source of adverse effects or therapeutic failure, certain drug-drug and drug-food interactions can result in beneficial pharmacokinetic outcomes that enhance therapeutic efficacy and safety. These interactions may be harnessed to improve bioavailability, extend plasma half-life, or reduce dosing frequency for drugs with narrow therapeutic windows or poor oral absorption. Beneficial drug-drug interactions can occur when one agent inhibits metabolic enzymes (e.g., cytochrome P450 isoforms) or efflux transporters (e.g., P-glycoprotein), thereby increasing the systemic exposure of a co-administered drug. For anti-retroviral drugs, the drug called ritonavir is used as an pharmacokinetic enhancer. Similarly, drug-food interactions—such as co-administration of high-fat meals with lipophilic drugs (e.g., posaconazole or fenofibrate)—can enhance absorption by improving solubilization and gastrointestinal retention. Citrus fruits like grapefruit inhibit intestinal CYP3A4, potentially increasing drug concentrations of certain statins or calcium channel blockers. Mechanistically, these interactions may involve enzyme inhibition, transporter modulation, or membrane permeability enhancement. When clinically predictable and well-managed, such interactions can be used to reduce drug costs, improve patient adherence, and increase therapeutic response. This shows the positive potential of selected pharmacokinetic drug-drug and drug-food interactions. Understanding these mechanisms allows clinicians and pharmacists to optimize drug therapy through evidence-based use of co-administered agents and dietary strategies.