Relationship of apparent systemic clearance to individual organ clearances: effect of pulmonary clearance and site of drug administration and measurement.

The relationships between apparent total-body clearance (CL) and individual organ clearances were mathematically defined with respect to the site of drug administration and measurement. The derived equations can be applied to drugs undergoing different pathways of elimination, including pulmonary clearance. A physiological pharmacokinetic model was used to test the validity of the equations. The apparent systemic clearance values obtained through the equations, using the individual organ clearance values, were identical to those calculated utilizing the model-generated data, indicating the validity of the equations. Furthermore, it was shown that the conventional estimation of CL of drugs subject to pulmonary clearance is highly dependent upon the site of drug administration and measurement. The relationships were further utilized to explain the reported CL values which are higher than the cardiac output. The equations developed here may be used to predict the contribution of different organs, such as the lungs, to the apparent systemic clearance of drugs.