A recirculatory model of the pulmonary uptake and pharmacokinetics of lidocaine based on analysis of arterial and mixed venous data from dogs

Tom C. Krejcie*, Michael J. Avram, W. Brooks Gentry, Claus U. Niemann, Mary P. Janowski, Thomas K. Henthorn

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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 for 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 (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.

Original languageEnglish (US)
Pages (from-to)169-190
Number of pages22
JournalJournal of Pharmacokinetics and Biopharmaceutics
Volume25
Issue number2
DOIs
StatePublished - 1997

Keywords

  • Antipyrine
  • Arteriovenous difference
  • Dogs
  • Indocyanine green
  • Lidocaine
  • Physiologic models
  • Pulmonary uptake
  • Tissue distribution

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Pharmacology (medical)

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