In this episode, we dive into the critical role of drug protein binding in pharmacokinetics and why it matters for patient care. Only the unbound, or free, fraction of a drug is pharmacologically active...available for distribution, metabolism, and elimination. We explore how highly protein-bound drugs, often bound to albumin, act as reservoirs, influencing drug half-life and distribution. Changes in protein binding, due to conditions like hypoalbuminemia or drug-drug interactions, can dramatically alter free drug concentrations, risking treatment failure or toxicity. Through real-world case examples involving valproic acid, furosemide, and ceftriaxone, we reveal how understanding protein binding is essential for safe and effective therapy.

Some Common Highly Protein-Bound Drugs and Their Approximate Binding Percentages:

Anticoagulants:

• Warfarin (~99% bound)

Antiepileptics:

• Phenytoin (~90–95% bound)

• Valproic acid (~90–95% bound)

• Carbamazepine (~75–80% bound)

NSAIDs:

• Naproxen (~99% bound)

• Diclofenac (~99% bound)

• Ibuprofen (~99% bound)

Cardiovascular drugs:

• Verapamil (~95% bound)

• Propafenone (~95% bound)

• Amiodarone (~96% bound)

• Furosemide (~95% bound)

Antibiotics:

• Ceftriaxone (~85–95% bound)

• Erythromycin (~90% bound)

• Clindamycin (~90% bound)

• Sulfonamides (Sulfamethoxazole) (~90–95% bound)

• Ertapenem (~85–95% bound)

Psychotropics / Others:

• Diazepam (~98% bound)

• Tolbutamide (~96% bound)

• Clozapine (~95% bound)

• Fluoxetine (~95% bound)