Insulin detemir achieves its prolonged duration of action (18–24 hours) primarily through which mechanism?
- A Formation of hexamers at the injection site that slowly dissociate into monomers
- B Acylation with a C14 fatty acid enabling reversible binding to albumin in plasma and the interstitium ✓
- C Substitution of asparagine by glycine at A21, creating an isoelectric point shift causing microprecipitation at physiological pH
- D PEGylation of the B-chain reducing renal clearance and extending plasma half-life
Correct answer: B. Acylation with a C14 fatty acid enabling reversible binding to albumin in plasma and the interstitium
Explanation
Insulin detemir has a C14 fatty acid (myristic acid) attached to lysine B29, enabling reversible albumin binding in the subcutaneous tissue and plasma. This albumin-buffering effect slows absorption and distribution, producing a prolonged, peakless action profile. Glargine (not detemir) achieves its long action via isoelectric precipitation (option C). Hexamer formation is the mechanism for NPH (protamine zinc) insulin.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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