Drug handling by the lungs

Population pharmacokinetics/pharmacodynamics of anesthetics

“…Model misspecification occurs when the ordinarily applied linear compartmental models do not adequately approximate the underlying physiology. 12 During the first minutes of drug administration, compartmental models, therefore, provide inadequate input for PD models. Recirculatory models have been developed by Krejcie et al 13 in which the pulmonary and peripheral intravascular and extravascular subsystems, each consisting of volumes and time delays, are connected according to circulatory physiology.…”

Preclinical Study of Potential Antiglioma Novel Tetrahydroisoquinoline Analogs: Pharmacokinetics and Mechanism of Action10.21007/etd.cghs.2012.0191

“…Measurement of the afferent-efferent arterial (pulmonary artery vs. aorta) concentrations in steady states during a long intravenous infusion can be used in future study to confirm this finding in vivo [100,102]. Comparing AUC after intravenous or intra-aortic short-term infusion is more convenient method to examine effect of lung on drug disposition.…”

“…The first extrahepatic mechanism deserving consideration is the pulmonary metabolism [100][101][102]. The lung contains various CYP450 enzymes as well as phase II drug metabolism enzymes [103][104][105][106][107][108].…”

“…The lung contains various CYP450 enzymes as well as phase II drug metabolism enzymes [103][104][105][106][107][108]. It has the potential of metabolizing many foreign chemicals to a vast array of metabolites with different pharmacological and toxicological properties [100,102,109,110]. Intravenously dosed drugs are subject to pulmonary metabolism before entering the liver.…”

“…Comparing AUC after intravenous or intra-aortic short-term infusion is more convenient method to examine effect of lung on drug disposition. However, in some case, lung tissue may act as a deep compartment, which drugs will bind to and will not be released before end of blood sampling [100,102]. The afferent-efferent concentrations measurement can assure that the binding sites in lungs are saturated after long infusion and thus will not mistakenly count lung retention as lung clearance.…”