Potential pitfalls in the conventional pharmacokinetic studies: effects of the initial mixing of drug in blood and the pulmonary first-pass elimination.

The classical concept of assuming that an i.v. dose instantaneously distributes into the central or plasma compartment is reviewed, as is the potential for pulmonary first-pass effect. Based on available literature, the concept is shown to lead to serious errors in estimating pharmacokinetic parameters, particularly for drugs with high clearance.