生物活性

• 描述Angiotensin-converting enzyme (ACE) is helpful in controling blood pressure and converting the hormone angiotensin I to be active. Captopril is an ACE inhibitor with IC₅₀ of 6 nM which can reduce the risk of doubling the serum creatinine concentration by almost 50% in patients and also be helpful in renal dysfunction therapy and blood pressure reduction. Besides, Captopril can also be used for the treatment of diabetic nephropathy and left ventricular dysfunction. This drug can reach to peak hypotensive effect in 1 - 1.5 hrs with about 30% protein binding ratio and serum half-life of 2 hrs^[1]. LNM35 cells treated with captopril of concentrations from 0.01 to 10 mM for 24 hrs showed inhibitory impact on the cell viability at all these concentrations, the differences were significant in the concentrations of 0.1, 1 and 10 mM. While LNM35 cells treated with captopril of concentrations from 0.001 to 10 mM in FBS buffer for 24 - 48 hrs demonstrated induction of cell apoptosis from 2.5% for control group to 9% and 15.5% for captopril-treated cells, respectively. The higher of the captopril concentrations, the more of the apoptosis induction. NMRI female nude mice with about 100 mm³ tumors were treated with 2.8 mg captopril per mouse and the results showed that the human tumor xenografts growth was significantly reduced by 52% and 58% at the 18 and 21 days respectively. Furthermore, the mean lymph node weight was 63.5 mg in the captopril-treated group, smaller than that in the control group (127mg). Captopril also decreased the tumor cell proliferation by assessing the levels of the nuclear antigen K_i-67 in K_i-67-positive cells^[2].

• 动物研究
  剂量	Mice: 1.2 mg/kg, 12 mg/kg[3] (p.o.) Rat: 30 mg/kg[4] (p.o.), 100 mg/kg[5] (p.o.); 12.5 mg/kg - 50 mg/kg[6] (i.p.)
  给药途径	p.o., i.p.
  动物药代数据	Animal Rats[7] Dose 10 mg/kg Administration p.o. T1/2 1.8578 ± 3.67 h Tmax 0.16 h AUCtot 99.11 ± 13.05 ng·h/ml Cmax 100.63 ± 28.62 ng/ml

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02631148	Obesity Predi... more >>abetic State Collapse <<	Phase 3	Recruiting	January 2018	United States, Massachusetts ... more >> Brigham and Women's Hospital Recruiting Boston, Massachusetts, United States, 02215 Contact: Fatima Adigun, MPH    617-264-3071    fadigun-bello@partners.org Collapse <<
  NCT01427049	-	-	Completed	-	Netherlands ... more >> UMC Utrecht Utrecht, Netherlands Collapse <<
  NCT02200822	Heart Failure (HF)	Phase 4	Unknown	July 2017	Belgium ... more >> Ziekenhuis Oost Limburg Recruiting Genk, Limburg, Belgium, 3600 Contact: Petra Nijst, MD    3289761525    nijst.petra@gmail.com    Contact: Wilfried Mullens, MD, PhD    3289327110    wilfried.mullens@zol.Be    Principal Investigator: Petra Nijst, MD          Principal Investigator: Frederik Verbrugge, MD          Principal Investigator: Matthias Dupont, MD          Principal Investigator: Wilfried Mullens, MD, PhD Collapse <<

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• 参考文献

• [1] Zaman MA, Oparil S, et al. Drugs targeting the renin-angiotensin-aldosterone system. Nat Rev Drug Discov. 2002;1(8):621-36.

  [2] Attoub S, Gaben AM, et al. Captopril as a potential inhibitor of lung tumor growth and metastasis. Ann N Y Acad Sci. 2008.

  [3] Kanda T, Inoue M, et al. Low-dose combination therapy with metoprolol and captopril for congestive heart failure in mice. Cardiovasc Drugs Ther. 1993 Nov;7(5):795-800.

  [4] Larivière R, Lebel M, et al. Effects of losartan and captopril on endothelin-1 production in blood vessels and glomeruli of rats with reduced renal mass. Am J Hypertens. 1998 Aug;11(8 Pt 1):989-97.

  [5] Antonaccio MJ, Rubin B, et al. Effects of captopril on vascular reactivity of SHR in vivo and in vitro. Hypertension. 1981 Nov-Dec;3(6 Pt 2):II-211-5.

  [6] Boskabadi J, Mokhtari-Zaer A, et al. The effect of captopril on lipopolysaccharide-induced lung inflammation. Exp Lung Res. 2018 May - Jun;44(4-5):191-200.

  [7] Siska S, Mun Im A, et al. Effect of Apium graveolens Extract Administration on the Pharmacokinetics of Captopril in the Plasma of Rats. Sci Pharm. 2018 Feb 16;86(1). pii: E6.

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