Nossaman B C, Amouzadeh H R, Sangiah S
Department of Physiological Sciences, College of Veterinary Medicine, Oklahoma State University, Stillwater 74078-0353.
Vet Hum Toxicol. 1990 Jun;32(3):216-9.
The effects of chloramphenicol, cimetidine and phenobarbital on the xylazine-ketamine anesthesia and the development of tolerance to xylazine-ketamine and xylazine were studied in dogs. The duration of absence of pedal reflex, duration of return of consciousness, and duration for return of ambulation were determined. Pretreatment with chloramphenicol (33 mg/kg, iv, 15 min) and cimetidine (5 mg/kg, iv, 24 h) did not influence any of the above parameters significantly. Phenobarbital pretreatment (15 mg/kg, iv, 96 h) significantly reduced the duration of anesthesia. Although not significant, there is a trend toward the development of tolerance to repeated administration of xylazine (1.1 mg/kg, iv) and ketamine (10 mg/kg, iv) combination and xylazine (1/1 mg/kg, iv) alone once daily at 3 d intervals for 9 d. These results indicate that hepatic cytochrome P-450 drug metabolizing enzymes, inhibited by chloramphenicol and cimetidine, might not be involved in the metabolism of xylazine and/or ketamine, phenobarbital inducible hepatic cytochrome P-450 enzymes might play a role in metabolic disposition of xylazine and/or ketamine, and repeated administration of xylazine alone or in combination with ketamine might lead to development of tolerance in dogs.
研究了氯霉素、西咪替丁和苯巴比妥对犬赛拉嗪-氯胺酮麻醉的影响以及犬对赛拉嗪-氯胺酮和赛拉嗪耐受性的发展。测定了足趾反射消失时间、意识恢复时间和行走恢复时间。氯霉素（33mg/kg，静脉注射，15分钟）和西咪替丁（5mg/kg，静脉注射，24小时）预处理对上述任何参数均无显著影响。苯巴比妥预处理（15mg/kg，静脉注射，96小时）显著缩短了麻醉时间。尽管不显著，但每天一次以3天的间隔重复静脉注射赛拉嗪（1.1mg/kg）和氯胺酮（10mg/kg）的组合以及单独静脉注射赛拉嗪（1/1mg/kg），持续9天，有产生耐受性的趋势。这些结果表明，受氯霉素和西咪替丁抑制的肝细胞色素P-450药物代谢酶可能不参与赛拉嗪和/或氯胺酮的代谢，苯巴比妥诱导的肝细胞色素P-450酶可能在赛拉嗪和/或氯胺酮的代谢处置中起作用，单独重复静脉注射赛拉嗪或与氯胺酮联合使用可能导致犬产生耐受性。
