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.
D000818:Animals; D001711:Biotransformation; D001798:Blood Proteins / Q000378:metabolism; D002302:Cardiac Output; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008168:Lung / Q000378:metabolism*; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D011485:Protein Binding; D013997:Time Factors
D001798:Blood Proteins; D004364:Pharmaceutical Preparations