Kukanich Butch
College of Veterinary Medicine, Kansas State University, 228 Coles Hall, Manhattan, KS 66506-5802, USA.
Vet Clin North Am Exot Anim Pract. 2011 Jan;14(1):1-20. doi: 10.1016/j.cvex.2010.09.006.
The treatment and prevention of pain in zoologic companion animals is difficult because of the lack of data available on the safety and efficacy of analgesics. Pharmacokinetic (PK)-pharmacodynamic (PD) studies integrate changes in drug concentrations and changes in the drug's effect. All experimental studies assessing the PDs of analgesics have limitations in animals, but the data provided by experimental studies are valuable in designing dosages. Placebo-controlled, randomized, and blinded clinical trials provide the best PK and PD data, but are rarely performed in major veterinary species because of the number of animals required for the study, lack of preliminary PK and PD data in a given species, species-specific differences in PK and PD, and ethical and toxicologic concerns. The usefulness and limitations as well as considerations for interpreting PK, PD, and controlled clinical studies are discussed. An example of allometric analysis of buprenorphine in mammals is also included.
由于缺乏有关镇痛药安全性和有效性的数据,对伴侣动物疼痛的治疗和预防颇具难度。药代动力学(PK)-药效学(PD)研究整合了药物浓度变化和药物效应变化。所有评估镇痛药药效学的实验研究在动物身上都存在局限性,但实验研究提供的数据在设计剂量方面具有重要价值。安慰剂对照、随机且双盲的临床试验能提供最佳的PK和PD数据,但由于研究所需动物数量、特定物种缺乏初步PK和PD数据、PK和PD的物种特异性差异以及伦理和毒理学问题,这类试验在主要兽医物种中很少进行。本文讨论了PK、PD以及对照临床研究的实用性、局限性和解读时的注意事项。还包括了布托啡诺在哺乳动物中的异速生长分析实例。