Example : Determination of gentamicin pharmacokinetic parameters showed that the elimination rate constant is 0.27 hr-1 and the volume of distribution is 12 L. Recommend a dosing regimen that should achieve steady state maximum and minimum plasma conc of 6 and 1 mg/L in this patient.
Dosage regimen design
a- Determination of dosing interval
1 mg/L = 6 mg/L e -0.27 hr -1(τ-t')hr
6 mg/L =
Ko(1-e-0.27 hr -1 1hr)
0.27 hr -1 12L (1-e-0.27 hr -1 8hr)
You can solve for Ko and the dose
1 mg/L = 6 mg/L e-0.27 hr -1(τ-t')hr
τ-t' = 6.6 hr if t' = 1 hr
τ = 7.6 hr Then τ = 8 hr
6 mg/L =
Ko(1-e-0.27 hr -1 1hr)
0.27 hr -1 12L (1-e-0.27 hr -1 8hr)
Ko = 72.7 mg/hr
If t' = 1 hr, the dose = 72.7 mg
Regimen: 75 mg of gentamicin given as a short iv infusion of 1 hr every 8 hours.
By substitution for the dose and dosing
interval in the equations for the maximum
and minimum conc at s.s., the actual conc
should be 6.2 mg/L and 0.94 mg/L. The
difference between the desired and the
actual conc resulted from approximation of the
dose and dosing interval.
