Dosing Regimen Design (Cont’d)

b- IV and fast-release oral formulations

During repeated administration of iv and fast-release oral formulations, large fluctuations in the plasma concentrations are observed. The steady state maximum and minimum plasma concentrations have to be within the therapeutic range.

i- Selection of the dosing interval

The desired maximum and minimum plasma conc at steady state are selected based on the therapeutic range of the drug.

Assume that the desired steady state maximum and minimum plasma conc are 20mg/L and 10mg/L, respectively.

MTC
MEC
Cpmax ss = 20 mg/L
Cpmin ss = 10 mg/L
MTC
MEC
The dosing interval is the time
required for the maximum conc
to decline to the minimum conc
Cpmin ss= Cp max ss e - κ τ

Substitution for the desired maximum and minimum conc and the estimated k of the drug, allows determination of the time (τ) required for Cpmax ss to decline to Cpmin ss.

The calculated τ should be rounded to the nearest practical dosing interval (6 hr, 8 hr, 12 hr, 18 hr, 24 hr, 48 hr, etc.)