A Recirculatory Model of the Pulmonary Uptake and Pharmacokinetics of Lidocaine Based on Analysis of Arterial and Mixed Venous Data from Dogs

Authors: Krejcie T.C.1; Avram M.J.1; Brooks Gentry W.1; Niemann C.U.1; Janowski M.P.1; Henthorn T.K.1

Source: Journal of Pharmacokinetics and Pharmacodynamics, Volume 25, Number 2, April 1997 , pp. 169-190(22)

Publisher: Springer

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Abstract:

Pulmonary uptake of basic amine xenobiotics such as lidocaine may influence the onset of drug effect and ameliorate toxicity. To date, pharmacokinetic analysis of pulmonary drug uptake has been only semiquantitative and ill-suited for relating pharmacodynamics to pharmacokinetics or jar estimating the time course of the fraction of drug dose residing in the lung during a single pass. We have developed recirculatory models in an experiment in which lidocaine was injected into the right atrium simultaneously with markers of intravascular space (indocyanine green) and total body water (antipyrine): this was followed by rapid arterial and mixed venous blood sampling. Such models are interpretable physiologically and are capable of characterizing the kinetics of the pulmonary uptake of lidocaine in addition to peripheral tissue distribution and elimination. The apparent pulmonary tissue volume of lidocaine (39 ml/kg) was nearly ninefold greater than that of antipyrine (4.5 ml/kg). The recirculatory model characterized both arterial and mixed venous data, but the latter data were not essential for estimating lidocaine's pulmonary disposition either before or after recirculation of drug was evident.

Keywords: indocyanine green; antipyrine; lidocaine; tissue distribution; dogs; pulmonary uptake; physiologic models; arteriovenous difference

Document Type: Research article

Affiliations: 1: Northwestern University Medical School, Department of Anesthesiology, CH—WI39, 303 E. Chicago Avenue, Chicago, Illinois 60611 3008

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