Aminoglycoside Pharmacokinetics and Pharmacodynamics

Population-Based Dosing

Questions provided by Michele Splinter, Pharm.D.

A 78 year old male is admitted to the hospital with sepsis secondary to a UTI with gram-negative organisms seen on gram stain of urine. His admission weight is 177 lbs, and he is 5' 8" tall. He has chronic renal insufficiency which is stable with an admission serum creatinine of 1.624 mg/dl. The physician decides to start gentamicin and wants to obtain peak serum concentrations of 8 mg/L and trough serum concentrations of 1 mg/L or less. Assume a volume of distribution of 0.25 L/kg based on dosing weight. Based on your knowledge of estimation of creatinine clearance and gentamicin elimination rate constant [kel (hr-1) = 0.01 + 0.0024 (CLcr in mL/min)], calculate kel, t1/2, Vd, CL. What loading dose (rounded down to the nearest 10 mg), maintenance dose (round down to the nearest 10 mg) and dosing interval (up to the nearest 12 hr) would you recommend? Infusion duration should be fixed at 1 hour.

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Some Equations:

IBW equation (male)
Equation 27.4.1 IBW for Male Patients

IBW equation (female)
Equation 27.4.2 IBW for Female Patients

Creatine Clearance C-G Equation
Equation 27.4.3 Creatinine Clearance (Cockcroft-Gault Equation)

Dosing Interval
Equation 27.4.4 Dosing Interval, τ

Maintenance Dose
Equation 27.4.5 Maintenance Dose

Loading Dose
Equation 27.4.6 Loading Dose

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