What is the estimated pre‑dose gentamicin concentration (Cmin) for a 6‑year‑old child with normal renal function receiving gentamicin 2.5 mg/kg every 8 hours, given a measured trough of 0.5 µg/mL taken 1 hour before the next dose and an elimination‑rate constant of 0.34 h⁻¹?

Estimated Pre-Dose Gentamicin Concentration (Cmin)

The estimated true pre-dose concentration (Cmin) is approximately 0.35 µg/mL, calculated by back-extrapolating the measured trough of 0.5 µg/mL collected 1 hour before the next dose using the elimination rate constant of 0.34 h⁻¹.

Pharmacokinetic Calculation

The measured concentration was obtained 1 hour before the scheduled dose, meaning it represents a level at time = -1 hour relative to the true trough (time = 0). To estimate the actual Cmin, use first-order elimination kinetics:

C(t) = C₀ × e^(-Ke × t)

Rearranging to solve for the concentration at the next dose time:

Cmin = Cmeasured × e^(-Ke × Δt)

Where:

• Cmeasured = 0.5 µg/mL
• Ke = 0.34 h⁻¹
• Δt = 1 hour (time from measurement to next dose)

Cmin = 0.5 × e^(-0.34 × 1) = 0.5 × e^(-0.34) = 0.5 × 0.712 ≈ 0.36 µg/mL

Clinical Interpretation for Pediatric Gentamicin Therapy

This estimated Cmin of 0.36 µg/mL is within the recommended therapeutic target of <0.5–1 µg/mL for minimizing nephrotoxicity while maintaining efficacy. 1, 2

Target Trough Concentrations

• For synergy-based regimens (endocarditis): Target trough <1 µg/mL, preferably <0.5 µg/mL 3, 1
• The American Heart Association explicitly recommends trough concentrations <1 µg/mL when gentamicin is dosed in 3 divided doses for endocarditis 3, 2
• The European Society of Cardiology recommends even stricter targets of <0.5 mg/L to minimize nephrotoxicity 1

Critical Monitoring Considerations

A true trough must be drawn immediately before the next scheduled dose—samples obtained 1 hour early represent mid-interval levels and require pharmacokinetic back-calculation as demonstrated above. 1

• Peak concentrations should be measured 30–60 minutes after infusion completion, targeting 3–4 µg/mL for synergy regimens in endocarditis 3, 1, 2
• Renal function monitoring is mandatory at least twice weekly during gentamicin therapy 1
• For pediatric patients receiving gentamicin 2.5 mg/kg every 8 hours (total 7.5 mg/kg/day), this dosing falls within the recommended 3–6 mg/kg/day range for synergy-based therapy 1

Common Pitfalls to Avoid

• Do not treat an 8-hour post-dose level or any non-pre-dose sample as a true trough—it cannot substitute for proper trough monitoring and requires mathematical correction 1
• Do not use once-daily dosing for endocarditis—multiple divided doses (every 8 hours) are mandatory for synergy-based regimens 3, 1, 2
• Do not continue therapy without documented peak levels—therapeutic efficacy cannot be confirmed without verifying adequate peak concentrations 1, 2

Dose Adjustment Decision

With an estimated Cmin of 0.36 µg/mL, no dose adjustment is required if the patient has normal renal function and the peak concentration is within target range (3–4 µg/mL). 3, 1, 2 However, if the creatinine clearance is <50 mL/min, dose reduction and extended intervals are mandatory regardless of measured levels. 3, 4