Gardner Sarah Y, Atkins Clarke E, Sams Richard A, Schwabenton A Brooke, Papich Mark G
Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, 4700 Hillsborough Street, Raleigh, NC 27606, USA.
J Vet Intern Med. 2004 Mar-Apr;18(2):231-7. doi: 10.1892/0891-6640(2004)18<231:cotpap>2.0.co;2.
The pharmacokinetics of enalapril (0.5 mg/kg i.v.) and the pharmacodynamics of enalapril (0.5 mg/kg PO) in 5 mares were investigated. After single i.v. dosing, concentrations of enalapril and enalaprilat, its active metabolite, were measured. Two weeks later, enalapril was administered by nasogastric tube. Potassium, creatinine, blood urea nitrogen (BUN), enalapril, and enalaprilat concentrations and angiotensin converting enzyme (ACE) activity were measured in serum. In addition, heart rate, blood pressure, digital venous blood gases, and lactate were measured. Two weeks later, enalapril was again administered by nasogastric tube. To mimic activation of the renin-angiotensin-aldosterone system, angiotensin I (0.5 microg/kg) was administered at fixed intervals, followed by blood-pressure and heart-rate measurement. The elimination half lives of enalapril and enalaprilat were 0.59 and 1.25 hours, respectively, after i.v. administration. After PO administration, enalapril and enalaprilat were not detectable in serum. There was a tendency (P = .0625) toward a decrease in ACE activity 45-120 minutes after enalapril administration, but ACE activity suppression was never > 16%. There was a tendency (P = .0625) toward a decrease in mean arterial pressure (MAP) 6-8 hours after enalapril administration. Serum concentrations of potassium, creatinine, and BUN and digital venous blood gases and lactate concentrations did not change. In response to angiotensin I, there was a tendency (P = .0625) toward a decrease in the MAP response 4-24 hours after enalapril administration. Single-dose enalapril at 0.5 mg/kg PO did not demonstrate significant availability, pharmacodynamic effect, or substantial suppression of ACE activity.
研究了5匹母马中依那普利（静脉注射0.5mg/kg）的药代动力学以及依那普利（口服0.5mg/kg）的药效学。单次静脉给药后，测定了依那普利及其活性代谢产物依那普利拉的浓度。两周后，通过鼻胃管给予依那普利。测定血清中的钾、肌酐、血尿素氮（BUN）、依那普利、依那普利拉浓度以及血管紧张素转换酶（ACE）活性。此外，还测量了心率、血压、指静脉血气和乳酸。两周后，再次通过鼻胃管给予依那普利。为模拟肾素-血管紧张素-醛固酮系统的激活，每隔固定时间给予血管紧张素I（0.5μg/kg），随后测量血压和心率。静脉给药后，依那普利和依那普利拉的消除半衰期分别为0.59小时和1.25小时。口服给药后，血清中未检测到依那普利和依那普利拉。依那普利给药后45 - 120分钟，ACE活性有下降趋势（P = 0.0625），但ACE活性抑制从未超过16%。依那普利给药后6 - 8小时，平均动脉压（MAP）有下降趋势（P = 0.0625）。血清钾、肌酐和BUN浓度以及指静脉血气和乳酸浓度未发生变化。在给予血管紧张素I后，依那普利给药后4 - 24小时，MAP反应有下降趋势（P = 0.0625）。口服0.5mg/kg的单剂量依那普利未显示出显著的生物利用度、药效学效应或对ACE活性的实质性抑制。
