1. Cardioprotective effect of fimasartan, a new angiotensin receptor blocker, in a porcine model of acute myocardial infarction
Jeong Gwan Cho, Jung Chaee Kang, Ari Chong, Hae Chang Jeong, Doo Sun Sim, Jong Min Kim, Nam Sik Yoon, Kyung Seob Lim, Min Suk Kim, Jung Ha Kim, Hee Seung Bom, Ju Han Kim, Kye Hun Kim, Jong Chun Park, Dae Sung Park, Shi Hyun Ryu, Hyun Kuk Kim, In Seok Jeong, Keun Ho Park, Sang Gi Oh, Young Joon Hong, Ki Hong Lee, Hyun Ju Yoon, Sung Soo Kim, Hyung Wook Park, Myung Ho Jeong, Su Young Jang, Jae Yeong Cho, Youngkeun Ahn, Ho Chun Song, Jahae Kim J Korean Med Sci . 2015 Jan;30(1):34-43. doi: 10.3346/jkms.2015.30.1.34.
Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.
2. A validated stability-indicating RP-LC method for the simultaneous determination of amlodipine and perindopril in tablet dosage form and their stress degradation behavior under ICH-recommended stress conditions
Mehmet Gumustas, Sibel A Ozkan J AOAC Int . 2013 Jul-Aug;96(4):751-7. doi: 10.5740/jaoacint.11-010.
A stability-indicating RP-LC assay method was developed for the simultaneous determination of the cardiovascular drugs amlodipine and perindopril in the presence of degradation products generated from forced decomposition studies. The developed method is applicable for the determination of related substances in bulk drugs and simultaneous assay in a tablet pharmaceutical dosage form. Separation of the drugs and their degradation products was obtained using an RP Waters Spherisorb ODS1 column (250 x 4.6 mm id, 5 pm particle size) with the mobile phase acetonitrile-water (30 + 70, v/v) containing 15 mM phosphoric acid. The pH of the mobile phase was adjusted to 5.0. A flow rate of 1.2 mL/min was used for the separations, with detection at 215 nm. The chromatographic separation was performed at a column temperature of 45 degrees C. Atenolol was chosen as the internal standard. Amlodipine and perindopril were exposed to thermal, photolytic, hydrolytic, and oxidative stress conditions, and the stressed samples were analyzed by the proposed method. Degradation studies showed that both compounds were degraded under these stress conditions. The method was found to be stability-indicating and can be used for the routine analysis of amlodipine and perindopril in the studied combined tablet dosage form.
3. Cardioprotective action of perindopril versus candesartan in renovascular hypertensive rats
Shingo Seki, Takehiko Izumi, Masayuki Taniguchi, Seibu Mochizuki, Makoto Nagai, Kazuaki Horikoshi, Ikuo Taniguchi Cardiovasc Drugs Ther . 2004 Sep;18(5):353-62. doi: 10.1007/s10557-005-5059-7.
We investigated the effects of an angiotensin-converting enzyme inhibitor and an angiotensin II type 1 receptor blocker on cardiac hypertrophy in rats with renovascular hypertension. Renovascular hypertensive (Goldblatt) rats were surgically prepared from Wistar rats. Four weeks later, the rats showed a significant increase in blood pressure. At high doses, both the perindopril (1 mg/kg/day) and the candesartan (2 mg/kg/day) decreased the systolic pressure in these rats to the level of control Wistar rats. At low doses (perindopril 0.1 mg/kg/day and candesartan 0.1 mg/kg/day), these drugs lowered blood pressure to 85% of that in hypertensive rats. Echocardiographic and morphological studies revealed severe cardiac hypertrophy and fibrosis in untreated Goldblatt rats. High-dose treatment with both drugs suppressed the progression of hypertrophy and fibrosis. Also, low-dose perindopril prevented cardiac hypertrophy and fibrosis. In contrast, at the same levels of blood-pressure reduction, low-dose candesartan did not prevent cardiac fibrosis nor the upregulation of cardiac collagen types I and III mRNA observed in untreated Goldblatt rats. Atrial natriuretic peptide mRNA was up-regulated in untreated Goldblatt rats. These changes were significantly decreased by both doses of perindopril or the high dose of candesartan. Serum levels of angiotensin II and aldosterone were significantly higher in untreated Goldblatt rats. Both doses of perindopril inhibited activation of the renin-angiotensin system, whereas candesartan had weaker effects. In particular, serum aldosterone was 347 +/- 20 pg/ml in low-dose perindopril versus 1796 +/- 324 pg/ml in low-dose candesartan. These results suggest that there were no differences between the cardioprotective actions of perindopril and candesartan at high dosages. On the other hand, low-dose treatment with perindopril was more effective in preventing cardiac fibrosis than was low-dose treatment with candesartan, despite similar changes in blood pressure. It is possible that changes in aldosterone secretion are related to this difference.
