Modelling of initial distribution of drugs following intravenous bolus injection.

Based on a recirculatory pharmacokinetic model, a physiologically realistic definition of the initial distribution volume has been developed to characterize the overall distribution process occurring shortly after rapid bolus injection of a drug. This apparent volume of distribution, which refers to the peak right atrial blood concentration, depends on the cardiac output and basic pharmacokinetic parameters usually derived from the whole blood concentration vs time curve. The initial distribution process appears to be affected by changes in the variance of the distribution of residence times of the drug in the body. The influence of the site and time of early blood sampling on the estimated initial distribution volume is discussed. This relatively simple a priori model should prove useful in predicting to a first approximation the principal characteristics of the initial distribution process.