A patient with chronic renal failure on gentamicin develops worsening vestibular toxicity despite standard weight-based dosing. The pharmacokinetic parameter most responsible for aminoglycoside toxicity in this patient is:

• A Reduced volume of distribution concentrating aminoglycosides in renal tubular cells
• B Increased protein binding in uremic patients reducing free drug but causing toxicity by displacement
• C Uremia-induced increased aminoglycoside entry through the blood-labyrinth barrier
• D Reduced renal clearance leading to prolonged plasma half-life and elevated trough concentrations ✓

Explanation

Aminoglycosides are almost entirely eliminated by renal tubular secretion and glomerular filtration; in CKD, markedly reduced renal clearance extends the elimination half-life (normally 2-3 hours, rising to 30-60 hours in dialysis patients). Elevated trough concentrations correlate strongly with ototoxicity and nephrotoxicity since drug accumulates in the perilymph and renal cortex. Extended-interval dosing (once-daily) and careful trough monitoring are essential; in severe CKD dose interval adjustment is required.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.