Effect of dietary patterns on the blood/urine concentration of the selected toxic metals (Cd, Hg, Pb) in Korean children.

This study was aimed to examine the association the blood/urinary concentration of toxic metal (Hg, Pb, and Cd) with children's dietary patterns. This cross-sectional study included 1026 school children aged 8-17 years. Dietary patterns were defined using factor loading scores for 108 foods from a Semi-Quantitative Food Frequency Questionnaire. A high blood Hg level was found in boys with a high score in the 'fish' pattern (p = 0.02), and in girls with a high score in 'fruit' pattern (p = 0.04). The concentration of Pb was related to the 'imprudent' pattern in high school boys (p = 0.02). The effect of the 'vegetable' pattern on high excretion of urinary Cd was observed in low grade elementary (p = 0.04) and middle school students (p < 0.0001), and the effect of the 'fruit' pattern on the urinary Cd was observed in high grade elementary school students (p = 0.02). This study suggests that the concentration of selected toxic metals in blood/urine could be affected by children's dietary pattern.

The Relationship between Occupational Status and Physical Activity in Korea.

This study examined the association between occupational status and physical activity (PA) in Korea. A total of 9,000 Koreans age 10 to 89 years participated in the Korean Survey of Citizens' Sports Participation project in 2012. However, 3,851 participants were excluded from the analysis (housewives, students, and the jobless), providing a sample size of 5,149 participants (3,165 men and 1,984 women) for this study. The association between occupational status and PA was then evaluated using multivariate logistic regression analysis. The odds ratios (ORs; 95% confidence interval [CI]) for reporting at least weekly PA according to job intensity, after adjusting for sex and age, were as follows: moderate-intensity jobs, 1.164 [1.026, 1.320], p = .018; and vigorous-intensity jobs, 1.591 [1.318, 1.921], p < .001, compared with low-intensity jobs as a reference category. For PA intensity in low- and moderate-intensity jobs, after adjusting for sex and age, the ORs (95% CI) were as follows: low-intensity PA, 1.355 [1.033, 1.778], p = .028, moderate PA, 1.227 [1.096, 1.487], p = .002, and vigorous PA, 1.570 [1.213, 2.032], p < .001, compared with sedentary as a reference category. For the intensity of PA among participants with low- or vigorous-intensity jobs, after adjusting for sex and age, the ORs (95% CI) were as follows: low-intensity PA, 1.015 [0.649, 1.586], p = .948, moderate-intensity PA, 1.890 [1.416, 2.522], p < .001, and vigorous-intensity PA, 2.403 [1.395, 4.139], p = .002, compared with sedentary as a reference category. For the intensity of PA between moderate-intensity and vigorous-intensity jobs, after adjusting for sex and age, the ORs (95% CI) were as follows: low-intensity PA, 1.010 [0.759, 1.344], p = .945, moderate-intensity PA, 1.381 [1.136, 1.678], p = .001, and vigorous-intensity PA, 1.595 [1.023, 2.486], p = .039, compared to sedentary as a reference category. The presented findings show a strong association between occupational status and PA patterns for Koreans.

Development of 3D-QSAR CoMSIA models for 5-(biphenyl-2-yl)-1H-tetrazole derivatives as angiotensin II receptor type 1 (AT1) antagonists.

As a development strategy for backups of Fimasartan (1), a comparative molecular similarity indices analysis (CoMSIA) of a set of sixty-five 5-(biphenyl-2-yl)-1H-tetrazole derivatives has been performed to find out the pharmacophore elements for angiotensin II receptor type 1 (AT1) blockade. The most potent compound containing pyrimidin-4(3H)-one ring, Fimasartan (1) was used to align the molecules. As a result, we obtained 3D-QSAR model which provided good predictivity for both the training set (q(2)=0.846, r(2)=0.975) and the external test set (rpred(2)=0.980). This model would guide the design of backups for Fimasartan (1), a launched oral antihypertensive agent.

Synthesis and antihypertensive activity of pyrimidin-4(3H)-one derivatives as losartan analogue for new angiotensin II receptor type 1 (AT1) antagonists.

The discovery, in vitro and in vivo studies of the highly potent AT(1) antagonist 12a (BR-A-657, Fimasartan) antagonists are presented. A series of pyrimidin-4(3H)-one derivatives as losartan analogue were synthesized and evaluated for a novel class of AT(1) receptor antagonists. Among them, 12a containing thioamido moiety displayed both high in vitro functional antagonism and binding affinity [IC(50)=0.42 and 0.13 nM, respectively] and inhibited strongly in vivo AngII-induced pressor response in pithed rats with an ED(50) of 0.018 mg/kg. Moreover, in vivo evaluation in furosemide-treated rat and conscious renal hypertensive rat models and the pharmacokinetic study showed that 12a is a highly potent and orally active AT(1) selective antagonist having stronger in vivo potency than losartan.

Safety, tolerability, pharmacokinetics, and pharmacodynamics of fimasartan following single and repeated oral administration in the fasted and fed states in healthy subjects.

BACKGROUND AND OBJECTIVES: Fimasartan (BR-A-657) is a novel, non-peptide angiotensin II receptor antagonist with a selective type I receptor blockade effect. Two first-in-human studies investigated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of fimasartan. METHODS: Fasted single oral tablet doses of fimasartan 20-480 mg or placebo were administered to 40 healthy male subjects (aged 19-54 years) in a double-blind, randomized, sequential-group design. Subjects receiving fimasartan 240 mg also received the same treatment in the fed state after an interval of 7 days. In another study, oral tablet doses of fimasartan 120 and 360 mg or placebo were given once daily for 7 days to groups of eight fasted healthy male subjects (aged 20-55 years) in a double-blind, randomized, sequential-group design. Safety and tolerability were assessed. The PK and PD of fimasartan were also evaluated and compared for the different doses. RESULTS: Fimasartan was safe and well tolerated, but with an increased incidence of low BP and postural dizziness for the 360 mg dose after repeated administration. Fimasartan produced increases in plasma renin activity, angiotensin I and II, which were not dose dependent. Maximal increases occurred between 6 and 8 hours post-dose, lasting up to 48 hours. Fimasartan was absorbed rapidly after all doses and had a multiphasic distribution. Two peaks in the plasma concentration-time profile were observed in most subjects. Steady state was achieved after three doses, and accumulation was minimal after repeated doses for 7 days (24-30%). The effective half-life ranged from 9.84 to 13.2 hours. The systemic exposure of fimasartan was dose proportional, and no marked food effect was noted after administration of 240 mg in the fed state. Urinary excretion of fimasartan was very low (1.74-2.51%), suggesting non-renal elimination. CONCLUSION: Fimasartan had a good safety profile and was well tolerated after fasted single oral doses of 20-480 mg, a fed single oral dose of 240 mg, and fasted repeated oral doses of 120 and 360 mg in healthy subjects. In addition, the PK and PD of fimasartan in this population were well characterized. Further studies are needed to evaluate the safety, efficacy, and dose-response relationship of fimasartan in patients with hypertension.