Disease relevance of Cilazaprilat

• The present study was designed to examine whether an ACE inhibitor, cilazaprilat, directly protects cardiac myocytes against hypoxia/reoxygenation (H/R) injury [1].
• Although there were no significant differences in collateral flow during ischemia, infarct size in the cilazaprilat group was smaller than that in the control group (15.1+/-3.0% versus 46.7+/-4.2% of the area at risk, P<0.0001) [2].
• The ACE inhibitor cilazaprilat was administered into the coronary artery 10 minutes before coronary occlusion, and infusion was continued until 1 hour after reperfusion [2].
• Concerning, the bradykinin-evoked erythema, enalaprilat significantly potentiated the response, whereas cilazaprilat only caused a slight increase [3].

High impact information on Cilazaprilat

• In addition, cilazaprilat markedly enhanced the cGMP content in myocytes during hypoxia, and this augmentation in cGMP could be blunted by L-NMMA and methylene blue but not by aminoguanidine [1].
• Total cardiac Ang II-forming activity was only partially inhibited by cilazaprilat (4.1+/-0.1 fmol x min(-1) x mg[-1]) and on a larger extent by chymostatin (2.6+/-0.3 fmol x min(-1) x mg[-1]) compared with control values (5.6+/-0.4 fmol x min(-1) x mg[-1]) [4].
• In rings of coronary artery with endothelium, relaxations to bradykinin were potentiated by the ACE inhibitors cilazaprilat and perindoprilat [5].
• However, for endothelium-denuded organoids, medial [3H]-thymidine incorporation in the combined presence of Ang II and cilazaprilat was not significantly different from that in untreated controls [6].
• In superfusion-perfusion bioassay studies with femoral arteries, cilazaprilat augmented the release of nonprostanoid endothelium-derived relaxing factors caused by bradykinin [7].

Biological context of Cilazaprilat

• Vasodilation by cilazaprilat remained unchanged at 4wHT and 12wHT in both Epi and Endo [8].
• Irrespectively, CILA reduced the upregulation of P-selectin at the higher H2O2 concentration, indicating that this process is regulated independently of the cellular redox status [9].
• The effect of cilazaprilat (CILA, 10 micro M), an ACE inhibitor, on redox status, expression of the adhesion molecule P-selectin, and PMN adhesion under conditions of oxidative stress was investigated in cultured human umbilical vein endothelial cells (HUVECs) [9].
• The pharmacokinetics of cilazaprilat, and the inhibition of plasma ACE were investigated in 12 elderly and 12 young healthy volunteers [10].
• 3. When compared with placebo cilazaprilat lowered diastolic pressure and increased heart rate significantly [11].

Anatomical context of Cilazaprilat

• 1. ACE from rat lung and testis was characterized by radioligand binding studies using [125I]-Ro 31-8472, the radioiodinated hydroxy derivative of the potent ACE inhibitor cilazaprilat [12].
• To test this idea, we administered imidaprilat and cilazaprilat, respectively to the canine ischemic myocardium [13].
• In vitro effect of cilazaprilat on sodium-potassium transport systems in human erythrocytes [14].

Associations of Cilazaprilat with other chemical compounds

• Enalaprilat, but not cilazaprilat, increases inflammatory skin reactions in guinea-pigs [15].
• Like enalapril and ramipril it is a prodrug, and is hydrolysed after absorption to cilazaprilat, which has a long terminal phase elimination half-life permitting once daily administration [16].
• 1. The pharmacokinetics of cilazapril and its active metabolite, cilazaprilat, were investigated in a three-part crossover study in 12 healthy male volunteers aged 19-38 years, excluding one subject who withdrew from the study [17].
• 2. Intravenous infusion of 2 mg cilazaprilat resulted in a significant and short lasting inhibition of ACE as evidenced by a decrease of plasma angiotensin II and an increase in plasma renin activity [11].
• We conclude that cilazaprilat and enalaprilat are inhibitors of ACE associated with the vein wall, but there is no evidence for either drug of direct, ACE-independent, prostaglandin-mediated vasodilation [18].

Gene context of Cilazaprilat

• 1. Cilazapril is the monoethyl ester prodrug form of the di-acid cilazaprilat, a new angiotensin converting enzyme (ACE) inhibitor [19].
• 5. Urinary recovery data indicated an absolute bioavailability for cilazaprilat of 57% (range 45-75%) from oral cilazapril, but only 19% (range 8-40%) from oral cilazaprilat.(ABSTRACT TRUNCATED AT 250 WORDS)[17]

Analytical, diagnostic and therapeutic context of Cilazaprilat

• When cilazaprilat (3 micrograms/kg per minute) was infused into the bypass tube for 10 minutes after reduction of coronary blood flow due to partial occlusion of the bypass tube, coronary blood flow increased from 30 +/- 1 to 43 +/- 2 mL/100 g per minute despite there being no changes in coronary perfusion pressure (43 +/- 1 mm Hg) [20].
• After oral administration of a single dose of 2.5 mg cilazapril, the active diacid cilazaprilat appeared rapidly in the plasma (Tmax 2.0 +/- 0.2 h) [21].
• Quantitative determination of the angiotensin-converting enzyme inhibitor cilazapril and its active metabolite cilazaprilat in pharmaceuticals and urine by high-performance liquid chromatography with amperometric detection [22].

References