Khor K H, Campbell F E, Charles B G, Norris R L G, Greer R M, Rathbone M J, Mills P C
School of Veterinary Science, The University of Queensland, Gatton, Qld, Australia.
J Vet Pharmacol Ther. 2012 Oct;35(5):437-45. doi: 10.1111/j.1365-2885.2011.01342.x. Epub 2011 Oct 11.
This study compared the pharmacokinetic and pharmacodynamic profiles of an extemporaneously prepared (compounded) atenolol paste and suspension for oral administration, against the commercially available divided tablet in healthy cats. Eleven healthy cats (mean: age 4 ± 0.4 year, weight 5.0 ± 0.7 kg) were dosed twice-daily with 12.5 mg atenolol (tablet, paste or suspension) for 7 days in a randomized cross-over design with a 7-day wash-out period. On day 7, an electrocardiogram was performed before and immediately after stress provocation (jugular venipuncture) at prestudy screening, and at 2, 6 and 12 h after morning dosing. Systolic arterial blood pressure (BP) was assessed following the second electrocardiogram. Plasma was collected at prestudy screening, and at 1, 2, 6 and 12 h to measure atenolol plasma concentrations. Mean atenolol dose was 2.5 mg/kg (range: 2.1-3.3 mg/kg). Stress-induced rise in heart rate was attenuated (P < 0.05) at every time point compared to baseline for all formulations. Although the paste significantly attenuated stress-induced elevation in heart rate at all time points, the effect was not consistently equivalent to the tablet. The BP was not altered (P > 0.05) at any time point by any formulation. In conclusion, there were no significant differences (P > 0.05) in any of the pharmacokinetic parameters or pharmacodynamic profiles of the paste and suspension compared to the commercially available tablet.
本研究比较了临时配制(复方)的阿替洛尔口服糊剂和混悬剂与市售阿替洛尔分片剂在健康猫体内的药代动力学和药效学特征。采用随机交叉设计,对11只健康猫(平均年龄4±0.4岁,体重5.0±0.7 kg)每日给药两次,每次给予12.5 mg阿替洛尔(片剂、糊剂或混悬剂),共给药7天,洗脱期为7天。在第7天,于研究前筛查时以及早晨给药后2、6和12小时,在应激激发(颈静脉穿刺)前和激发后立即进行心电图检查。在第二次心电图检查后评估收缩动脉血压(BP)。在研究前筛查时以及1、2、6和12小时采集血浆,以测量阿替洛尔的血浆浓度。阿替洛尔的平均剂量为2.5 mg/kg(范围:2.1 - 3.3 mg/kg)。与基线相比,所有制剂在每个时间点应激诱导的心率升高均有所减弱(P < 0.05)。尽管糊剂在所有时间点均显著减弱了应激诱导的心率升高,但效果并不始终等同于片剂。任何制剂在任何时间点均未改变血压(P > 0.05)。总之,与市售片剂相比,糊剂和混悬剂的任何药代动力学参数或药效学特征均无显著差异(P > 0.05)。