A Reevaluation of Prazosin Pharmacokinetics in a Two-Compartment Model, the Apparent Volume of Distribution and Comparative Simulations in the One-Compartment Model

摘要

Published clinical data of Prazosin were reevaluated pharmacokinetically using explicit solutions to drug concentration as a function of total time for IV bolus injection, intermittent intravenous infusion and oral routes of administration in an open two-compartment model. In a novel way, the apparent volume of distribution was estimated from a two-compartment model and found to be close to the total body water suggesting that Prazosin is distributed in all tissues both extracellularly and intracellularly. In addition, extracting the value of the apparent volume of distribution from a two-compartment model allowed comparative simulations in the one-compartment model. It is shown that dosage calculations of Prazosin intermittent infusion can be safely performed using the simpler one-compartment model equations. Lastly, several additional time-dependent pharmacokinetic parameters e.g., the peak time in the central and peripheral compartment and non-steady state and steady state peak concentration and AUC were determined using series equations for all three routes of administration, as a function of dose number and total time upon multiple drug administrations in the two-compartment model. It is also the first time that steady-state plasma drug concentration equations were derived in a two-compartment mammillary model.