Direct measurement of chlormethiazole extraction by liver, lung and kidney in man.

LE Mather, WB Runciman, AH Ilsley, KR Thomson, AR Goldin

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Abstract

1 Chlormethiazole was used as a basal sedative for patients undergoing angiographic procedures. 2 Blood samples were drawn opportunistically to examine chlormethiazole extraction across liver, lungs and kidney. 3 Extraction across liver was typically 70‐80% and apparently unrelated to input concentrations. Evidence for extraction across lung and kidney was inconclusive but these could each be approximately 20%. 4 Pharmacokinetics of chlormethiazole derived from compartment models were in accord with previous reports and were characterised by a high total body clearance (1‐1.5 l/min). 5 Postural changes associated with the radiological procedures caused fluctuating blood concentrations which appear as noise in curve fitting procedures. 6 Pharmacokinetic properties derived from compartment theory cannot cope with these perturbations because of the restriction imposed by time averaging (i.e. mean clearances, half‐lives and volumes are produced). Systematic studies of pharmacokinetic properties of perfusion‐limited drugs such as chlormethiazole must be developed in such a way as to allow for independent variation of flow and extraction. 1981 The British Pharmacological Society

Original languageEnglish
Pages (from-to)319-325
Number of pages7
JournalBritish Journal of Clinical Pharmacology
Volume12
Issue number3
DOIs
Publication statusPublished - 1 Jan 1981
Externally publishedYes

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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