Ziemniak J A, Shank R G, Schentag J J
Drug Metab Dispos. 1984 Mar-Apr;12(2):217-21.
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.
在犬类中研究了西咪替丁的药代动力学及脑脊液（CSF）分配情况。给4只健康雄性杂种犬静脉注射22mg/kg剂量的西咪替丁。犬类表现出与人类志愿者相似的代谢和药代动力学特征，西咪替丁在犬体内的总体清除率平均为7.5ml/（min·kg），而在人类中为7.7ml/（min·kg）。尸检组织浓度与在人类中测得的浓度相似。犬类和人类在任何药代动力学参数上均无统计学差异。西咪替丁亚砜是犬类中的主要代谢产物，与人类相似。通过西咪替丁脑脊液：血清曲线下面积之比确定的西咪替丁脑脊液分配系数为0.125±0.03。西咪替丁似乎通过被动扩散进入脑脊液，并通过被动扩散、脑脊液总体流动以及可能的主动转运过程被清除。我们得出结论，犬类是研究西咪替丁药代动力学的合适动物，也是研究H2拮抗剂脑脊液摄取的合适模型。
