The Time to Reach Steady State After the Administration of Intravenous Bolus, Constant Infusion, and Oral Immediate‐Release and Sustained‐Release Preparations

Abstract

Based on one‐compartment pharmacokinetic model, the equations to calculate the specific fractional steady‐state of drug level achieved at any time (FSS) after administration of intravenous bolus, constant infusion, and oral immediate‐release preparations are reviewed. Also the equation to calculate FSS after administering an oral sustained‐release dosage form is derived. From these equations, it can be shown that the drug FSS after these routes of administration is dependent primarily on the elimination rate constant (K). However, for a sustained‐release preparation, the FSS is dependent on K, drug release rate constant (K1), as well as the fraction of sustained release (Fs) of the dosage form. Using the new derived equation for FSS, several simulations were performed to evaluate the effects of K1 K, and Fs. These indicate that the time to achieve a given FSS is prolonged as K1 or K becomes smaller and as Fs becomes large.