Direct measurement of chlormethiazole extraction by liver, lung and kidney in man.
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.
D000368:Aged; D002719:Chlormethiazole / Q000378:metabolism*; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged
D002719:Chlormethiazole