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 (CLD) in this respect. METHODS: Since mammillary compartmental models are widely used, CLD 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 CLD allowed a comparison of distributional properties of different drugs and provided physiological insight. Significant changes in CLD were observed as a result of drug-drug interactions, transporter polymorphisms and a diseased state. CONCLUSION: Total distribution clearance CLD 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.