Ferré Pierre J, Pasloske Kirby, Whittem Ted, Ranasinghe Millagahamanda G, Li Qiang, Lefebvre Hervé P
UMR 181 Physiopathologie et Toxicologie Expérimentales INRA-ENVT, France.
Vet Anaesth Analg. 2006 Jul;33(4):229-36. doi: 10.1111/j.1467-2995.2005.00264.x.
To determine the pharmacokinetic parameters of alfaxalone in dogs after the intravenous (IV) administration of clinical and supra-clinical doses of a 2-hydroxypropyl-beta-cyclodextrin (HPCD) alfaxalone formulation (Alfaxan-CD RTU).
Prospective two-period crossover design. Animals Eight (four male and four female) young adult healthy Beagle dogs. Methods The steroid anaesthetic alfaxalone was administered IV at two doses in a crossover design (2 and 10 mg kg(-1)) with a washout period of 21 days. Blood samples were collected before and up to 8 hours after dosing. Plasma concentrations of alfaxalone were assayed using a liquid chromatograph/mass selective detector technique and analyzed to estimate the main pharmacokinetic parameters by noncompartmental analysis. Results were expressed as mean +/- SD.
The mean duration of anaesthesia from endotracheal intubation to extubation was 6.4 +/- 2.9 and 26.2 +/- 7.5 minutes, for the 2 and 10 mg kg(-1) doses, respectively. The plasma clearance of alfaxalone for the 2 and 10 mg kg(-1) doses differed statistically at 59.4 +/- 12.9 and 52.9 +/- 12.8 mL kg(-1) minute(-1), respectively (p = 0.008) but this difference was deemed clinically unimportant; the harmonic mean plasma terminal half-lives (t(1/2)) were 24.0 +/- 1.9 and 37.4 +/- 1.6 minutes respectively. The volume of distribution was between 2 and 3 L kg(-1) and did not differ between the two doses. No sex effect was observed.
Alfaxalone, as an HPCD formulation (Alfaxan-CD RTU) administered in the dog provides rapid and smooth induction of anaesthesia, satisfactory conditions for endotracheal intubation and a short duration of anaesthesia. There was no clinically significant modification of the pharmacokinetic parameters between sexes and between the clinical (2 mg kg(-1)) and supra-clinical (10 mg kg(-1)) doses.
在静脉注射临床剂量和超临床剂量的2-羟丙基-β-环糊精（HPCD）阿法沙龙制剂（Alfaxan-CD RTU）后，测定犬体内阿法沙龙的药代动力学参数。
前瞻性两期交叉设计。动物 八只（四只雄性和四只雌性）年轻成年健康比格犬。方法 采用交叉设计，以两种剂量（2和10 mg·kg⁻¹）静脉注射类固醇麻醉剂阿法沙龙，洗脱期为21天。给药前及给药后长达8小时采集血样。采用液相色谱/质量选择检测器技术测定阿法沙龙的血浆浓度，并通过非房室分析进行分析，以估算主要药代动力学参数。结果以平均值±标准差表示。
对于2和10 mg·kg⁻¹剂量，从气管插管到拔管的平均麻醉持续时间分别为6.4±2.9分钟和26.2±7.5分钟。2和10 mg·kg⁻¹剂量的阿法沙龙血浆清除率分别为59.4±12.9和52.9±12.8 mL·kg⁻¹·分钟⁻¹，差异有统计学意义（p = 0.008），但这种差异被认为在临床上不重要；谐波平均血浆末端半衰期（t₁/₂）分别为24.0±1.9分钟和37.4±1.6分钟。分布容积在2至3 L·kg⁻¹之间，两种剂量之间无差异。未观察到性别效应。
作为HPCD制剂（Alfaxan-CD RTU）给药的阿法沙龙能使犬迅速平稳地诱导麻醉，为气管插管提供满意条件，且麻醉持续时间短。性别之间以及临床剂量（2 mg·kg⁻¹）和超临床剂量（10 mg·kg⁻¹）之间的药代动力学参数无临床显著改变。
