A 62-year-old man with chronic kidney disease (eGFR 25 mL/min/1.73m²) is prescribed gentamicin 80 mg IV for a urinary tract infection. His serum creatinine is 3.2 mg/dL. On day 3 of therapy, his serum gentamicin peak level is 8 µg/mL (normal peak 4–10 µg/mL) but trough is 2.5 µg/mL (normal trough <2 µg/mL). Which pharmacokinetic parameter is primarily altered in this patient, leading to drug accumulation?

Explanation

## Pharmacokinetic Alteration in Renal Impairment **Key Point:** Gentamicin is an aminoglycoside eliminated almost entirely by glomerular filtration. In severe renal impairment (eGFR 25), renal clearance (CLr) is drastically reduced. ### The Problem - **Normal gentamicin CLr:** ~100 mL/min - **This patient's CLr:** ~25 mL/min (proportional to eGFR) - **Result:** Elimination half-life increases from ~2 hours (normal) to ~24–48 hours ### Why Trough is Elevated With standard dosing intervals (q8h or q12h) but prolonged t½, drug accumulates because each dose is not fully eliminated before the next dose is given. The trough level >2 µg/mL indicates inadequate washout between doses. ### Pharmacokinetic Equation **Clearance (CL) = Dose / AUC** When renal CL ↓, AUC ↑ → steady-state levels ↑ **Clinical Pearl:** Aminoglycosides require dose adjustment or interval prolongation in renal failure. Extended-interval dosing (e.g., 5–7 mg/kg q24–48h) is preferred over traditional q8h dosing to maintain efficacy while reducing nephrotoxicity risk.