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愈创甘油醚在驴体内的药代动力学及心肺效应

Pharmacokinetics and cardiopulmonary effects of guaifenesin in donkeys.

作者信息

Matthews N S, Peck K E, Mealey K L, Taylor T S, Ray A C

机构信息

Texas Veterinary Medical Center, Texas A&M University, College Station 77843, USA.

出版信息

J Vet Pharmacol Ther. 1997 Dec;20(6):442-6. doi: 10.1046/j.1365-2885.1997.00081.x.

Abstract

Five donkeys and three horses were given guaifenesin, intravenously, by gravity administration, until recumbency was produced. The time and dose required to produce recumbency, recovery time to sternal and standing were recorded. Blood samples were collected for guaifenesin assay at 10, 20, 30, 40, 50, 60 min, and 2, 3, 4 and 6 h after guaifenesin administration. Serum was analysed for guaifenesin using HPLC and pharmacokinetic values were calculated using a computer software package (RSTRIP). In donkeys, heart and respiratory rates and blood pressures were recorded before and at 5-min intervals during recumbency. Arterial blood samples were collected before and at 5 and 15 min intervals during recumbency for analysis of pH, CO2, and O2. ANOVA was used to evaluate dynamic data, while t-tests were used for kinetic values. Respiratory rate was decreased significantly during recumbency, but no other significant changes from baseline occurred. The mean (+/- SD) recumbency dose of guaifenesin was 131 mg/kg (27) for donkeys and 211 mg/kg (8) for horses. Recovery time to sternal (min) was 15 (SD, 11) for donkeys and 34 (SD, 1.4) for horses. Time to standing was 32 min for donkeys and 36 min for horses. Calculation of AUC (area under the concentration-time curve) microgram/mL) (dose-dependent variable) was 231 (SD, 33) for donkeys and 688 (SD, 110) for horses. The clearance (CL) (mL/h.kg) was 546 (SD, 73) for donkeys, which was significantly different from 313 (SD, 62) for horses. Mean residence time (MRT) (h) was 1.2 (SD, 0.1) for donkeys and 2.6 (SD, 0.5) for horses. Volume of distribution Vd(area) (mL/kg) was 678 (SD, 92) for donkeys and 794 (SD, 25) for horses. At the rate of administration used in this study, donkeys required less guaifenesin than horses to produce recumbency, but cleared it more rapidly.

摘要

给五头驴和三匹马静脉滴注愈创甘油醚,通过重力给药,直至它们卧倒。记录产生卧倒所需的时间和剂量、恢复到胸卧姿势和站立姿势的时间。在给予愈创甘油醚后的10、20、30、40、50、60分钟以及2、3、4和6小时采集血样用于愈创甘油醚分析。使用高效液相色谱法分析血清中的愈创甘油醚,并使用计算机软件包(RSTRIP)计算药代动力学值。在驴身上,记录卧倒前以及卧倒期间每隔5分钟的心率、呼吸频率和血压。在卧倒前以及卧倒期间每隔5和15分钟采集动脉血样用于分析pH值、二氧化碳和氧气。使用方差分析来评估动态数据,而使用t检验来分析动力学值。卧倒期间呼吸频率显著降低,但与基线相比没有其他显著变化。愈创甘油醚使驴卧倒的平均(±标准差)剂量为131毫克/千克(27),马为211毫克/千克(8)。驴恢复到胸卧姿势的时间(分钟)为15(标准差,11),马为34(标准差,1.4)。驴站立的时间为32分钟,马为36分钟。驴的浓度 - 时间曲线下面积(AUC)(微克/毫升)(剂量依赖性变量)计算值为231(标准差,33),马为688(标准差,110)。驴的清除率(CL)(毫升/小时·千克)为546(标准差,73),与马的313(标准差,62)有显著差异。驴的平均驻留时间(MRT)(小时)为1.2(标准差,0.1),马为2.6(标准差,0.5)。驴的分布容积Vd(area)(毫升/千克)为678(标准差,92),马为794(标准差,25)。在本研究使用的给药速率下,驴产生卧倒所需的愈创甘油醚比马少,但清除速度更快。

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