Relationships between steady state blood concentrations and cardiac output during intravenous infusions

The blood concentration of a drug at steady state can be calculated from the 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 referenced to any particular site within the circulation. In contrast, in recirculating systems, the relative sites of an infusion, the lungs and organs of elimination, and dilution in the cardiac output, produce concentration gradients in the blood. Equations that describe the relationship between the steady state concentrations of a drug in arterial, pulmonary artery, mixed venous and eliminating organ (e.g. liver or kidney) blood and the intrinsic clearance of the drug in the lungs and the eliminating organ were derived analytically. The concentrations at all sites were shown to be cardiac output dependent with the following exceptions: (1) in arterial blood, when the drug is highly extracted by the lungs, and (2) in eliminating organ blood when there is no lung clearance of the drug. The arterial and pulmonary artery concentrations will be least affected by cardiac output in the absence of lung clearance, and if the intrinsic clearance in the eliminating organ is substantially less than cardiac output.