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Direct measurement of chlormethiazole extraction by liver, lung and kidney in man.
Author(s) -
Mather LE,
Runciman WB,
Ilsley AH,
Thomson KR,
Goldin AR
Publication year - 1981
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.1981.tb01220.x
Subject(s) - pharmacokinetics , compartment (ship) , lung , medicine , extraction (chemistry) , blood flow , kidney , anesthesia , perfusion , chemistry , chromatography , oceanography , geology
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.