Distribution Clearance: Significance and Underlying Mechanisms

Abstract Purpose Evaluation of distribution kinetics is a neglected aspect of pharmacokinetics. This study examines the utility of the model-independent parameter whole body distribution clearance ( CL D ) in this respect. Methods Since mammillary compartmental models are widely used, CL D was calculated in terms of parameters of this model for 15 drugs. The underlying distribution processes were explored by assessment of relationships to pharmacokinetic parameters and covariates. Results The model-independence of the definition of the parameter CL D allowed a comparison of distributional properties of different drugs and provided physiological insight. Significant changes in CL D were observed as a result of drug-drug interactions, transporter polymorphisms and a diseased state. Conclusion Total distribution clearance CL D is a useful parameter to evaluate distribution kinetics of drugs. Its estimation as an adjunct to the model-independent parameters clearance and steady-state volume of distribution is advocated.