Byrem T M, Robinson T F, Boisclair Y R, Bell A W, Schwark W S, Beermann D H
Department of Animal Science, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853-4801.
J Anim Sci. 1992 Dec;70(12):3812-9. doi: 10.2527/1992.70123812x.
Pharmacokinetic parameters for the beta 2-adrenergic agonist, cimaterol (CIM), were determined in growing Holstein steers. Compartmental analysis was used after measurement of CIM in body fluids by affinity chromatography and HPLC using UV detection. Recoveries from spiked plasma and urine standards were 70 +/- 1.2% and 68 +/- 1.1%, respectively. The minimum detection level in plasma was 1 ng/mL and the average CV was 5.1% for concentrations that ranged from 1 to 30 ng/mL. Four steers (276 +/- 24 kg) received 15 mg of CIM by bolus intravenous injection. Plasma CIM levels declined in a biphasic manner with half-lives of 2.5 min for the distribution phase and 54 min for the elimination phase. A two-compartment open model was used to describe the disappearance of CIM and the following pharmacokinetic parameters were obtained: central compartment volume (Vc) = .76 L/kg, apparent volume of distribution (Vd) = 4.1 L/kg, and transfer rate constants from the central to peripheral compartment (k12) = .177/min, from the peripheral to central compartment (k21) = .054/min and elimination from the central compartment (kel) = .074/min. After 8 h, total urinary CIM accounted for only 18.3% of the administered dose. Results suggest that circulating concentrations of CIM in growing steers are influenced by its accumulation in an unidentified peripheral pool and its conversion into unknown metabolite(s) before elimination.
在生长中的荷斯坦公牛中测定了β2-肾上腺素能激动剂西马特罗（CIM）的药代动力学参数。通过亲和色谱法和使用紫外检测的高效液相色谱法测定体液中的CIM后，进行了房室分析。加标血浆和尿液标准品的回收率分别为70±1.2%和68±1.1%。血浆中的最低检测水平为1 ng/mL，浓度范围为1至30 ng/mL时的平均变异系数为5.1%。四头公牛（276±24 kg）通过静脉推注接受15 mg的CIM。血浆CIM水平呈双相下降，分布相半衰期为2.5分钟，消除相半衰期为54分钟。使用二房室开放模型描述CIM的消失情况，并获得了以下药代动力学参数：中央房室容积（Vc）=0.76 L/kg，表观分布容积（Vd）=4.1 L/kg，从中央房室到周边房室的转运速率常数（k12）=0.177/分钟，从周边房室到中央房室的转运速率常数（k21）=0.054/分钟，以及从中央房室的消除速率常数（kel）=0.074/分钟。8小时后，尿中CIM总量仅占给药剂量的18.3%。结果表明，生长中的公牛体内CIM的循环浓度受其在一个未明确的周边池中的蓄积以及在消除前转化为未知代谢物的影响。
