van Griensven J M, Schoemaker R C, Cohen A F, Luus H G, Seibert-Grafe M, Röthig H J
Centre for Human Drug Research, University Hospital Leiden, The Netherlands.
Eur J Clin Pharmacol. 1995;47(6):513-8. doi: 10.1007/BF00193704.
The pharmacokinetics and pharmacodynamics of the prodrug ramipril and its active ACE-inhibiting metabolite ramiprilat were investigated in an open, randomised, three-way cross-over study in 12 healthy male volunteers. Subjects received 2.5 mg ramipril orally, 2.5 mg ramipril intravenously and 2.5 mg ramiprilat intravenously. The absolute bioavailability as judged by ramipril plasma AUC was 15%, by ramiprilat plasma AUC, 44%. Ramiprilat formation from intravenous ramipril was 53% and from oral ramipril 28%. Urinary recovery of oral ramipril was 23%, i.v. ramipril 49%, and i.v. ramiprilat 68% of the given dose. Maximum ACE inhibition was highest (100%) after i.v. ramiprilat; it was 99% after i.v. ramipril and 84% following oral ramipril. ACE inhibition over 24 h was highest after i.v. ramipril, 2% less with i.v. ramiprilat and 34% less with oral ramipril. Ramiprilat renal clearance was concentration dependent. The biological availability of ramipril can best be judged by ramiprilat AUC, urinary recovery of ramipril and metabolites, or ACE inhibition over 24 h. It is concluded that the bioavailability of oral ramipril seems to be in the range of 44-66%.
在一项针对12名健康男性志愿者的开放性、随机、三交叉研究中，对前体药物雷米普利及其具有活性的血管紧张素转换酶（ACE）抑制代谢产物雷米普利拉的药代动力学和药效动力学进行了研究。受试者分别口服2.5毫克雷米普利、静脉注射2.5毫克雷米普利以及静脉注射2.5毫克雷米普利拉。根据雷米普利的血浆曲线下面积（AUC）判断，其绝对生物利用度为15%；根据雷米普利拉的血浆AUC判断，绝对生物利用度为44%。静脉注射雷米普利后雷米普利拉的生成率为53%，口服雷米普利后为28%。口服雷米普利的尿回收率为给药剂量的23%，静脉注射雷米普利为49%，静脉注射雷米普利拉为68%。静脉注射雷米普利拉后最大ACE抑制率最高（100%）；静脉注射雷米普利后为99%，口服雷米普利后为84%。24小时内的ACE抑制率在静脉注射雷米普利后最高，静脉注射雷米普利拉后低2%，口服雷米普利后低34%。雷米普利拉的肾清除率与浓度有关。雷米普利的生物利用度最好通过雷米普利拉的AUC、雷米普利及其代谢产物的尿回收率或24小时内的ACE抑制率来判断。得出的结论是，口服雷米普利的生物利用度似乎在44%至66%的范围内。
