PT  - JOURNAL ARTICLE
AU  - J A Ziemniak
AU  - R G Shank
AU  - J J Schentag
TI  - The partitioning of cimetidine into canine cerebrospinal fluid.
DP  - 1984 Mar 01
TA  - Drug Metabolism and Disposition
PG  - 217--221
VI  - 12
IP  - 2
4099  - http://dmd.aspetjournals.org/content/12/2/217.short
4100  - http://dmd.aspetjournals.org/content/12/2/217.full
SO  - Drug Metab Dispos1984 Mar 01; 12
AB  - The pharmacokinetics and cerebrospinal fluid (CSF) partitioning of cimetidine were studied in the dog. Four healthy male mongrel dogs were given a 22 mg/kg iv dose of cimetidine. The dogs demonstrated metabolic and pharmacokinetic characteristics similar to human volunteers, as the total body clearance of cimetidine averaged 7.5 ml/min/kg in the dog as compared to 7.7 ml/min/kg in humans. Autopsy tissue concentrations were similar to those measured in humans. There were no statistical differences between dogs and humans in any pharmacokinetic parameters. Cimetidine sulfoxide was the major metabolite in the dog, similar to that in humans. Cimetidine CSF partitioning, as determined by the ratio of cimetidine CSF:serum area under the curve was 0.125 +/- 0.03. Cimetidine appears to enter the CSF by passive diffusion, and is removed by passive diffusion, CSF bulk flow, and possibly by an active transport process. We conclude that the dog is an appropriate animal to investigate cimetidine pharmacokinetics and is a suitable model for examining the CSF uptake of H2-antagonists.