Relationships between steady state blood concentrations and cardiac outputduring intravenous infusions

The blood concentration of a drug at steady state can be calculated from th e ratio of infusion rate over the total body drug clearance. When the blood is assumed to be a homogenous pool, the clearance is not usually reference d to any particular site within the circulation. Ln contrast, in recirculat ing systems, the relative sites of an infusion, the lungs and organs of eli mination, and dilution in the cardiac output, produce concentration gradien ts in the blood. Equations that describe the relationship between the stead y state concentrations of a drug in arterial, pulmonary artery, mixed venou s and eliminating organ (e.g. liver or kidney) blood and the intrinsic clea rance of the drug in the lungs and the eliminating organ were derived analy tically. The concentrations at all sites were shown to be cardiac output de pendent with the following exceptions: (1) in arterial blood,when the drug is highly extracted by the lungs, and (2) in eliminating organ blood when t here is no lung clearance of the drug. The arterial and pulmonary artery co ncentrations will be least affected by cardiac output in the absence of lun g clearance, and if the intrinsic clearance in the eliminating organ is sub stantially less than cardiac output. Copyright (C) 2000 John Wiley & Sons, Ltd.