Dosage Intervals Based on Mean Residence times

Abstract

It is shown that a suitable dosage interval, τ, can be estimated by a factor times the sum of the mean residence time (MRT) of the central compartment (MRTC) and the MRT of the absorption site (MRTA). This value of τ will provide a ratio, maximum steady-state plasma concentration; minimum steady-state plasma concentration, which averages ˜2, such that the percent variation of the steady-state drug concentration is ±33%. It is shown that this approach produces vastly improved steady-state concentrations compared with those obtained when the τ value is chosen as equal to the apparent elimination half-life, which, classically, has been the approach usually used. When the drug is administered intravenously, the MRT of the absorption site in the above relationship is equal to zero. Suitable values of the “factor” in the above relationship were found to be 0.75 for the two-compartment open models with bolus iv administration, unity for the one-compartment open model with first-order absorption and elimination, and 1.35 for the classical two-compartment open model with first-order absorption.