• Toxicological Research
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• 제29권3호
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• pp.217-219
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• 2013

Hypertension is a serious health problem due to high frequency and concomitant other diseases including cardiovascular and renal dysfunction. Olmesartan cilexetil is a new antihypertensive drug associated with angiotensin II receptor antagonist. This study was conducted to evaluate the mutagenicity of olmesartan cilexetil by bacterial reverse mutation test using Salmonella typhimurium (TA100, TA1535, TA98, and TA1537) and Escherichia coli (WP2 uvrA). At the concentrations of 0, 62, 185, 556, 1667, and 5000 ${\mu}g$/plate, olmesartan cilexetil was negative in both Salmonella typhimurium and Escherichia coli regardless of presence or absence of metabolic activation system (S9 mix). These results demonstrate that olmesartan cilexetil does not induce bacterial reverse mutation.

• The Korean Journal of Physiology and Pharmacology
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• 제14권4호
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• pp.241-248
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• 2010

The present sutdy aimed to determine whether olmesartan, an angiotensin II (Ang II) type 1 ($AT_1$) receptor blocker, can influence the CA release from the isolated perfused model of the rat adrenal medulla. Olmesartan ($5{\sim}50{\mu}M$) perfused into an adrenal vein for 90 min produced dose- and time-dependent inhibition of the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM, a direct membrane-depolarizer), DMPP (100 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Olmesartan did not affect basal CA secretion. Also, in adrenal glands loaded with olmesartan (15 ${\mu}M$), the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}M$, an activator of voltage-dependent L-type $Ca^{2+}$ channels), cyclopiazonic acid (10 ${\mu}M$, an inhibitor of cytoplasmic $Ca^{2+}$-ATPase), veratridine (100 ${\mu}M$, an activator of voltage-dependent $Na^+$ channels), and Ang II (100 nM) were markedly inhibited. However, at high concentrations ($150{\sim}300{\mu}M$), olmesartan rather enhanced the ACh-evoked CA secretion. Taken together, these results show that olmesartan at low concentrations inhibits the CA secretion evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by direct membrane depolarization from the rat adrenal medulla, but at high concentrations it rather potentiates the ACh-evoked CA secretion. It seems that olmesartan has a dual action, acting as both agonist and antagonist at nicotinic receptors of the isolated perfused rat adrenal medulla, which might be dependent on the concentration. It is also thought that this inhibitory effect of olmesartan may be mediated by blocking the influx of both $Na^+$ and $Ca^{2+}$ into the rat adrenomedullary chromaffin cells as well as by inhibiting the $Ca^{2+}$ release from the cytoplasmic calcium store, which is thought to be relevant to the $AT_1$ receptor blockade, in addition to its enhancement on the CA secreton.

• 폴리머
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• 제39권1호
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• pp.33-39
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• 2015

올메사탄은 BCS 2단계에 해당하는 약물로 물에 잘 녹지 않는 난용성 약물이다. 이런 약물이 낮은 생체이용률과 제형을 설계하는 과정에서 어려움을 주는 원인이 된다. 본 연구에서는 올메사탄을 분무건조법 및 회전용매증 발법을 이용해 고체분산체를 제조하여 제법에 따른 난용성약물의 용출률을 확인하였다. 수용성 고분자로 PVP를 사용하여 약물과 고분자의 비율별로 고체분산체를 제조하였다. SEM을 이용하여 고체분산체의 형태학적인 특성을 분석하였고, 고체분산체의 결정학적 성질은 XRD와 DSC를 통하여 확인하였다. 또한 FTIR을 통해 화학적인 변화를 확인하고, 생체 외 용출거동 실험을 통하여 변화된 용출률을 확인하였다. 제조된 고체분산체는 pH 1.2에서 용출을 확인하였으며, 올메텍과 용출률을 비교하였으며, 분무건조를 통해 약물의 용출률을 향상시킬 수 있다는 것을 확인할 수 있다.

• 통합자연과학논문집
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• 제10권1호
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• pp.20-26
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• 2017

Chemerin receptor, which predominantly expressed in immune cells as well as adipose tissue, was found to stimulate chemotaxis of dendritic cells and macrophages to the site of inflammation. Chemerin is a widely distributed multifunctional secreted protein implicated in immune cell migration, adipogenesis, osteoblastogenesis, angiogenesis, myogenesis, and glucose homeostasis. Recent studies suggest chemerin may play an important role in the pathogenesis of obesity and insulin resistance and it becomes a potential therapeutic target for treating type II diabetes. The crystal structure of chemerin receptor has not yet been resolved. Therefore, in the present study, homology modelling of CMKLR1 was done utilizing the crystal structure of human angiotension receptor in complex with inverse agonist olmesartan as the template. Since the template has low sequence identity, we have incorporated both threading and comparative modelling approach to generate the three dimensional structure. 3D models were generated and validated. The reported models can be used to characterize the critical amino acid residues in the binding site of CMKLR1.

• Kidney Research and Clinical Practice
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• 제37권4호
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• pp.373-383
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• 2018

Background: Several epidemiologic studies have suggested that the urine sodium excretion (USE) can be estimated in lieu of performing 24-hour urine collection. However, this method has not been verified in patients with chronic kidney disease (CKD) or in an interventional study. The purpose of this study was to evaluate the usefulness of estimating USE in a prospective low-salt diet education cohort (ESPECIAL). Methods: A new formula was developed on the basis of morning fasting urine samples from 228 CKD patients in the ESPECIAL cohort. This formula was compared to the previous four formulas in the prediction of 24-hour USE after treatment with olmesartan and low-salt diet education. Results: Most previously reported formulas had low predictability of the measured USE based on the ESPECIAL cohort. Only the Tanaka formula showed a small but significant bias (9.8 mEq/day, P < 0.05) with a low correlation (r = 0.34). In contrast, a new formula showed improved bias (-0.1 mEq/day) and correlation (r = 0.569) at baseline. This formula demonstrated no significant bias (-1.2 mEq/day) with the same correlation (r = 0.571) after 8 weeks of treatment with olmesartan. Intensive low-salt diet education elicited a significant decrease in the measured USE. However, none of the formulas predicted this change in the measured urine sodium after diet adjustment. Conclusion: We developed a more reliable formula for estimating the USE in CKD patients. Although estimating USE is applicable in an interventional study, it may be unsuitable for estimating the change of individual sodium intake in a low-salt intervention study.

• Childhood Kidney Diseases
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• 제27권2호
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• pp.121-126
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• 2023

The administration of angiotensin type 2 receptor blockers (ARBs) during pregnancy is known to cause ARB fetopathy, including renal insufficiency. We aimed to analyze the outcomes of two patients who survived ARB fetopathy and perform an accompanying literature review. Case 1 was exposed antenatally from a gestational age of 30 weeks to valsartan because of maternal pregnancy-induced hypertension. The patient presented with oliguria immediately after birth, and renal replacement therapy was administered for 24 days. Seven years after birth, renal function was indicative of stage 2 chronic kidney disease (CKD) with impaired urinary concentration. Case 2 had a maternal history of hypertension and transient ischemic attack and was treated with olmesartan until 30 weeks of pregnancy. Renal replacement therapy was performed for 4 days since birth. After 8 years, the patient is with CKD stage 2, with intact tubular function. Recent reports suggest that ARB fetopathy might manifest as renal tubular dysgenesis and nephrogenic diabetes insipidus, in contrast to mild alterations of glomerular filtration. Tubular dysfunction may induce CKD progression and growth retardation. Patients with ARB fetopathy should be monitored until adulthood. The ARB exposure period might be a critical factor in determining the severity and manifestations of fetopathy.

• 한국임상약학회지
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• 제22권4호
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• pp.330-339
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• 2012

Background : Hypertension is treated with both lifestyle modification and pharmacotherapy. The Seventh Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7), published in 2003, provides a streamlined management approach to hypertension for the primary care physician. The JNC-7 is the gold standard also in Korea. According to the JNC-7, special therapeutic considerations are recommended for high-risk individuals with compelling indications. The presence of compelling indications in any given patient should be considered when selecting specific pharmacotherapy to treat hypertension. However, in patients with compelling indications, it is unknown that hepatotoxicity is caused by Calcium Channel Blocker (CCB), one of 1st anti-hypertensive drugs. Now, the CCB is the most used 1st anti-hypertensive drug in Korea Therefore, we evaluated the changes in blood liver function parameters (ALT, AST, Total bilirubin, serum albumin) for the study group. Methods : We randomly collected and retrospectively analyzed Electronic Medical Record data (n=28,788) of patients, and who took calcium channel blockers(non-dihydropyridines; diltiazem, verapamil, dihydropyridines; amlodipine, barnidipine, benidipine, clinidipine, efonidipine, felodipine, isradipine, lacidipine, lercanidipine, nicardipine, nifedipine, nimodipine), with having liver function tests (LFTs) from July 1st 2009 to June 30th 2010 at the Seoul National University Hospital in Korea. Control groups are two antihypertensive agents: RAS blockade (ARB; candesartan, irbesartan, losartan, olmesartan, telmisartan, valsartan, ACE-I; cilazapril, enalapril, fosinopril, imidapril, perindopril, ramipril) and, Diuretics (loop; furosemide, torsemide, thiazide; hydrochlorothiazide[HCTZ], indapamide). Patients not having LFT results at these three standard points of time(baseline, during, medication, and after finishing medication) were excluded. The collected data were analyzed by using the SPSS (Version12.0) and Microsoft Excel (Version2007). Results : 711 patients who were treated CCB (297), RAS blockade (232) or Diuretics (182) monotherapy were selected for the study. In selected patients, liver damage degree(changes of each LFTs value) was higher in diuretics group than other groups, followed by RAS blockade and CCB. In diuretics group's was loop-diuretics group was higher than thiazide-diuretics group. In CCB group, Nondihydropyridine-CCB's damage degree was higher than Dihydropyrine-CCB's that. Conclusions : Despite the limitations due to the retrospective study, among patients with abnormal LFTs, the use of CCBs led to a less liver damage than other 1st anti-hypertensive agents. It can be recommended CCBs as one of the initial treatments of hypertension in patients with liver disease.