Insulin glargine has a prolonged, peakless action profile compared with regular insulin. The pharmacokinetic basis for this is:
- A It is formulated at pH 4 and precipitates in the neutral subcutaneous tissue, forming microprecipitates that slowly dissolve and release monomers ✓
- B It contains zinc-protamine complexes that dissociate very slowly at physiological pH after subcutaneous injection
- C It has a fatty acid acylation that binds albumin in the subcutaneous depot, prolonging absorption
- D It is a hexameric preparation that must first dissociate into dimers and monomers before absorption, but does so more slowly than other long-acting insulins
Correct answer: A. It is formulated at pH 4 and precipitates in the neutral subcutaneous tissue, forming microprecipitates that slowly dissolve and release monomers
Explanation
Insulin glargine is engineered with two additional arginine residues at the B-chain C-terminus and a glycine substitution at position A21, shifting its isoelectric point to approximately pH 5.4–6.7. It is formulated in an acidic solution (pH 4); on injection into the neutral pH of subcutaneous tissue, it precipitates into microcrystalline deposits. These dissolve slowly and consistently, releasing insulin monomers continuously without a pronounced peak. Insulin degludec, by contrast, uses fatty acid acylation for albumin binding.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.