• Journal of Pharmaceutical Investigation
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• v.39 no.2
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• pp.107-110
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• 2009

To investigate the interaction and skin damage of valsartan with polysorbate 80, the physical mixture of valsartan and polysorbate 80 was prepared and then its adhesion, dispersibility, DSC and skin damage in nude rats were investigated. The physical mixture of valsartan and polysorbate 80 appeared as an aggregated form and could hardly be dispersed in water. The DSC curve showed that physical mixture disappeared the intrinsic peaks of valsartan and polysorbate 80 at about $115^{\circ}C$ and $170^{\circ}C$, respectively. It appeared a new relatively broad endothermic peak at about $150^{\circ}C$, suggesting that valsartan was chemically interacted with polysorbate 80. Furthermore, it induced the severe skin irritation and damage in nude mice. Thus, polysorbate 80 must not be used in the preparation of valsartan-loaded pharmaceutical dosage forms.

• KSBB Journal
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• v.31 no.4
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• pp.219-227
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• 2016

Valsartan, a drug for the treatment of cardiovascular disease, exhibited low bioavailability which was caused by, at least in part, limited solubility at low pH. Present investigation deals with the preparation and characterization of gastro-retentive drug delivery system (GRDDS) using valsartan solid dispersion. We prepared solid dispersion using surfactants (Poloxamer 407) and alkalizer ($Na_2CO_3$) which may to be useful for improving solubility of valsartan at low pH and evaluated by saturated solubility of valsartan in distilled water. Valsartan gastro-retentive (GR) tablets containing solid dispersion prepared and evaluated by weight variation, floating time and dissolution rate. Compression at lower pressures resulted in the tablets floating over simulated gastric fluid (pH 1.2) for more than 17 h. In vitro release of valsartan from GR tablet was dependent on the amount of poloxamer 407 and hydroxypropyl methylcellulose. On the basis of evaluation parameter, formulation E-3 was selected as a final formulation. Therefore, it can be concluded that the GR tablets containing solid dispersion may be exploited successfully for the delivery of poorly drug such as valsartan.

• Journal of Pharmaceutical Investigation
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• v.39 no.3
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• pp.173-176
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• 2009

A new crystal form of valsartan dipotassium was isolated by recrystallization using the one-pot method. The new crystal form was identified as a monohydrate form ($C_{24}H_{27}N_5O_3K_2.H_2O$) and characterized by diffential scanning calorimetry (DSC), thermogravimetric analysis (TGA) and X-ray powder diffractometry (PXRD). The new crystal data demonstrated to be clearly different from those known for the tetrahydrate form ($C_{24}H_{27}N_5O_3K_2.4H_2O$). It was observed that the monohydrate of vasartan dipotassium salt was completely dissolved in water within 1 hour and its dissolution rate was much faster than anhydrous free form of valsartan.

• Journal of Environmental Analysis, Health and Toxicology
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• v.21 no.4
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• pp.304-315
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• 2018

Located in Gimhae, Hwapo is the biggest riverine wetland in the province of Gyeongsangsam-do, Korea, and is a major habitat for various species. However, it is suspected that various pollutants enter the wetlands from agricultural and industrial areas. This study identifies major organic pollutants in this wetland and their sources using high performance liquid chromatography-high resolution mass spectrometry during one summer season. Forty-five substances were selected for quantitative analysis using target screening, and other non-selected compounds were screened using suspect and non-target screening methods. The results were that 21 and 17 targeted substances were detected in July and August, respectively. Major pollutants in July and August were oxadiazon (July: 17-220 ng/L, August: 66-460 ng/L), carbendazim (July: 10-110 ng/L, August: 64-520 ng/L), caffeine (July: 33-1,100 ng/L, August: 56-580 ng/L), and niflumic acid (July: 23-75 ng/L, August: 42-290 ng/L). Sampling sites S4 in July and S2 in August were the major inflow points. Ten substances (tricyclazole, hexaconazole, diuron, fexofenadine, irbesartan, simetryn, cimetidine, valsartan, tebuconazole, and benzotriazole) and four metabolites (valsartan acid, azoxystrobin acid, TEB_M324c, and 2-aminobenzimidazole) were tentatively identified through suspect and non-target screening, respectively.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.4
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• pp.299-307
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• 2015

Severe acute pancreatitis (SAP) is normally related to multiorgan dysfunction and local complications. Studies have found that local pancreatic renin-angiotensin system (RAS) was significantly upregulated in drug-induced SAP. The present study aimed to investigate the effects of angiotensin II receptors inhibitor valsartan on dual role of RAS in SAP in a rat model and to elucidate the underlying mechanisms. 3.8% sodium taurocholate (1 ml/kg) was injected to the pancreatic capsule in order for pancreatitis induction. Rats in the sham group were injected with normal saline in identical locations. We also investigated the regulation of experimentally induced SAP on local RAS expression in the pancreas through determination of the activities of serum amylase, lipase and myeloperoxidase, histological and biochemical analysis, radioimmunoassay, fluorescence quantitative PCR and Western blot analysis. The results indicated that valsartan could effectively suppress the local RAS to protect against experimental acute pancreatitis through inhibition of microcirculation disturbances and inflammation. The results suggest that pancreatic RAS plays a critical role in the regulation of pancreatic functions and demonstrates application potential as AT1 receptor antagonists. Moreover, other RAS inhibitors could be a new therapeutic target in acute pancreatitis.

• Childhood Kidney Diseases
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• v.27 no.2
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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.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.5
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• pp.467-472
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• 2015

Histone deacetylase (HDAC) has been recognized as a potentially useful therapeutic target for cardiovascular disorders. However, the effect of the HDAC inhibitor, trichostatin A (TSA), on vasoreactivity and hypertension remains unknown. We performed aortic coarctation at the inter-renal level in rats in order to create a hypertensive rat model. Hypertension induced by abdominal aortic coarctation was significantly suppressed by chronic treatment with TSA (0.5 mg/kg/day for 7 days). Nicotinamide adenine dinucleotide phosphate-driven reactive oxygen species production was also reduced in the aortas of TSA-treated aortic coarctation rats. The vasoconstriction induced by angiotensin II (Ang II, 100 nM) was inhibited by TSA in both endothelium-intact and endothelium-denuded rat aortas, suggesting that TSA has mainly acted in vascular smooth muscle cells (VSMCs). In cultured rat aortic VSMCs, Ang II increased p66shc phosphorylation, which was inhibited by the Ang II receptor type I ($AT_1R$) inhibitor, valsartan ($10{\mu}M$), but not by the $AT_2R$ inhibitor, PD123319. TSA ($1{\sim}10{\mu}M$) inhibited Ang II-induced p66shc phosphorylation in VSMCs and in HEK293T cells expressing $AT_1R$. Taken together, these results suggest that TSA treatment inhibited vasoconstriction and hypertension via inhibition of Ang II-induced phosphorylation of p66shc through $AT_1R$.

• Korean Journal of Clinical Pharmacy
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• v.22 no.4
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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.