Abstract
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.
DMD articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|