Distribution Clearance: Significance and Underlying Mechanisms

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.

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.

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.

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.