Dosing Optimization of Aminoglycosides

Clinical Pharmacokinetics
PHDR 321
(Homework-I) Answers

Question 1. Y.F is a 75-year-old, 62-kg (176 cm) male with gram-negative sepsis. His current
serum creatinine is 1.2 mg/dL, and. Compute a gentamicin dose given as IV infusion over one
hour for this patient to provide a steady-state peak concentration of 9 μg/mL and a steady-state
trough concentration of 1.5 μg/mL using conventional dosing.

1. IBW=22 × ([the actual patient’s height in meters]^2)

=68 kg
2. Creatinine Clearance (ml/min) = [(140 − age)IBW] / (72 ⋅ SCr)
3. Ke (Gentamicin) = 0.00293(CrCl) + 0.014
=0.16 h1
4. VD = 0.3 L/Kg
= 18.6
5. Dosage interval (τ) using a 1-hour infusion= τ = [(ln Cssmax − ln Cssmin) / ke] + t′
= 12 hours
6. Maintenance dose using IV infusion= X0 = Cssmax ke V [(1 − e−keτ) / (1 − e−ket′)]
= X0 = 160 mg
Question 2. Y.F is a 75-year-old, 62-kg (176 cm) male with gram-negative sepsis. was prescribed
gentamicin 110 mg every 12 hours. Steady-state gentamicin concentrations where peak
concentration was 9.5 μg/mL while the trough concentration was 2.2 μg/mL were obtained.
Compute a revised gentamicin dose for this patient to provide a steady-state peak concentration
of 8 μg/mL and a steady state trough concentration of 1 μg/mL using conventional dosing.

Dosenew= (Css, new/ Css, old)*dose old

= (8/9.5)*110
= 90 mg every 12 hours

Question 3. N.F is a 29-year-old, 62-kg (176 cm) male with gram-negative sepsis. was prescribed
gentamicin 500 once daily. Steady-state gentamicin concentrations was 11.5 μg/mL 6 hours after
dose was given. Compute a revised gentamicin dose for this patient to provide a steady-state
peak concentration of < 10 μg/mL and a steady state trough concentration of < 2 μg/ using The
Hartford Nomogram Method.

Answer
The from the graph above the gentamicin was obtained at time 7 and it was 11.5 μg/mL, the
revised dose would be 500 mg every 48 hours or every other day