Dohoo S, Tasker R A, Donald A
Department of Anatomy and Physiology, Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, Canada.
J Vet Pharmacol Ther. 1994 Dec;17(6):426-33. doi: 10.1111/j.1365-2885.1994.tb00273.x.
The pharmacokinetics of single-dose morphine sulphate (MS) administered intravenously (i.v.) and intramuscularly (i.m.) and of oral sustained-release morphine sulphate (OSRMS) were studied in dogs. Beagles (n = 6) were randomly assigned to six treatment groups using a Latin square design. Treatments included MS 0.5 and 0.8 mg/kg i.v. and i.m. and OSRMS 15 and 30 mg orally (p.o). Serum samples were drawn at intervals up to 420 min following parenteral MS and 720 min following OSRMS. Serum was analysed for morphine concentration using a radioimmunoassay. Pharmacokinetic analysis of the results revealed that MS was eliminated by a first-order process best described by a two-compartment model. For i.v. and i.m. data there were no statistically significant differences (P < 0.05) between steady-state volume of distribution, half-life of elimination and plasma clearance. As expected, area under the concentration vs. time curve (AUC) was significantly greater for the 0.8 mg/kg dosage for i.v. and i.m. routes, and time to maximum serum concentration was significantly longer following i.m. administration. For OSRMS there were no significant differences between dosage for any parameter (AUC, Cmax, tmax, t1/2, F) and prolonged absorption of the drug occurred over approximately 6 h. Bioavailability (F) for both oral dosages was approximately 20%. The i.m. route is an effective method for rapid and complete delivery of MS to dogs. OSRMS may be useful in the provision of long-term analgesic therapy in dogs, but further work is required to verify the safety and effectiveness of this preparation.
研究了静脉注射（i.v.）和肌肉注射（i.m.）单剂量硫酸吗啡（MS）以及口服缓释硫酸吗啡（OSRMS）在犬体内的药代动力学。使用拉丁方设计将比格犬（n = 6）随机分为六个治疗组。治疗包括静脉注射和肌肉注射0.5和0.8 mg/kg的MS以及口服（p.o.）15和30 mg的OSRMS。在注射非口服MS后长达420分钟以及口服OSRMS后720分钟内定期采集血清样本。使用放射免疫分析法分析血清中的吗啡浓度。对结果进行的药代动力学分析表明，MS通过双室模型描述的一级过程消除。对于静脉注射和肌肉注射数据，稳态分布容积、消除半衰期和血浆清除率之间无统计学显著差异（P < 0.05）。正如预期的那样，静脉注射和肌肉注射途径中0.8 mg/kg剂量的浓度-时间曲线下面积（AUC）显著更大，且肌肉注射给药后达到最大血清浓度的时间显著更长。对于OSRMS，任何参数（AUC、Cmax、tmax、t1/2、F）的剂量之间均无显著差异，且药物吸收延长约6小时。两种口服剂量的生物利用度（F）约为20%。肌肉注射途径是将MS快速、完全递送至犬体内的有效方法。OSRMS可能有助于为犬提供长期镇痛治疗，但需要进一步研究以验证该制剂的安全性和有效性。
