Insulin degludec (Tresiba) has a longer, flatter action profile than insulin glargine because of which pharmacokinetic property?
- A Formation of insoluble precipitate at physiological pH due to shift in isoelectric point
- B Formation of multi-hexameric depot chains at the injection site with slow dissolution, combined with strong albumin binding ✓
- C Fatty acid acylation preventing renal filtration and prolonging circulatory half-life
- D Polyethylene glycol modification (PEGylation) reducing receptor-mediated clearance
Explanation
Insulin degludec contains a C18 fatty diacid connected to the B29 lysine via a glutamic acid linker. After subcutaneous injection, zinc-containing hexamers self-associate into soluble multi-hexameric chains forming a large subcutaneous depot. These chains slowly dissolve monomers/dimers that then bind albumin in the interstitium and plasma, further prolonging action. The resulting ultra-long action (>42 hours) with minimal peak reduces nocturnal hypoglycemia. Insulin glargine works via pH-dependent precipitation (option A). PEGylation is used in some formulations of other biologics but not insulin degludec.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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