Pharmacokinetic Modelling of a Parent Drug and its Metabolite: Atracurium and Laudanosine

Vladimir Nigrovic, Mark Banoub

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

A pharmacokinetic model was designed to describe simultaneously the plasma concentrations of atracurium and its metabolite laudanosine. The proposed model satisfactorily fits the observations and is based on the assumptions that the parent drug spontaneously degrades to laudanosine at the rate comparable with that observed in vitro at pH 7.4 and 37°C; that 2 molecules of laudanosine are formed from 1 molecule of atracurium; that an initial very rapid decay of a fraction of the atracurium dose is responsible for the initially high plasma laudanosine concentrations; that the rapid disappearance of atracurium from plasma is accounted for by its spontaneous degradation and by the sequestration of atracurium in a deep compartment; and that laudanosine formed from atracurium is added to its central compartment, with its disposition described by a simple 2-compartment model with elimination from the central compartment. The model projects that about 43% of the atracurium dose is rapidly converted to laudanosine and that nearly the whole injected amount of atracurium is degraded to laudanosine.

Original languageEnglish (US)
Pages (from-to)396-408
Number of pages13
JournalClinical Pharmacokinetics
Volume22
Issue number5
DOIs
StatePublished - May 1992

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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