eng Oriental Scientific Publishing Company Biomedical and Pharmacology Journal 0974-6242 2026-06-29 19 2 72374 article Mohammad Shah Amran 1 Fareha Anan Shristy 2 Tashfiya Zaman Mouree 3 Saif Bin Salam Bondhon 4 Shaila Kabir 5 Fahima Aktar 5 Department of Pharmacy, School of Pharmacy and Public Health, Independent University, Bangladesh. Department of Pharmacy, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh. Department of Pharmacy, Atish Dipankar University of Science and Technology, Dhaka, Bangladesh. Department of Pharmacy, Bangladesh University of Professionals (BUP), Dhaka, Bangladesh. Molecular Pharmacology and Herbal Drug Research Laboratory, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Dhaka, Dhaka, Bangladesh. Protein binding is a fundamental determinant of drug pharmacokinetics and pharmacodynamics, influencing drug distribution, efficacy, toxicity, metabolism, and elimination. Most drugs interact with plasma proteins such as albumin, α1-acid glycoprotein (AAG), and lipoproteins, with the extent and nature of binding depending on physicochemical properties of the drug as well as physiological and pathological factors. Albumin predominantly binds acidic and neutral drugs, whereas AAG preferentially binds basic compounds. Lipoproteins serve as important carriers for highly lipophilic drugs, thereby affecting their distribution and clearance. The pharmacologically active fraction of a drug is the unbound portion, making protein binding a critical factor in determining therapeutic response and adverse effects. This review provides a comprehensive overview of the mechanisms and principles of drug-protein interactions, the major plasma proteins involved, and their influence on drug disposition. It further examines factors that alter protein binding, including disease states, age-related physiological changes, protein concentration variability, species differences, drug-drug interactions, food–drug interactions, and drug-metal interactions. The clinical implications of altered protein binding are discussed with reference to selected therapeutic agents, highlighting the importance of monitoring unbound drug concentrations in specific patient populations. By integrating classical concepts with recent advances in the understanding of plasma protein binding, this review underscores the pivotal role of drug–protein interactions in optimizing pharmacotherapy, improving therapeutic outcomes, and minimizing toxicity. https://biomedpharmajournal.org/vol19no2/pharmacology-of-protein-binding-of-drugs-an-extensive-review/ Albumin α1-Acid glycoprotein Drug disposition Drug interactions Drug-protein binding Lipoproteins Therapeutic drug monitoring