Effect of High- and Low-sodium Intake on the Pharmacokinetics and Pharmacodynamic Effects of Fimasartan

The study design is a two-diet, two-period, two-sequence, randomized, open label and cross-over with 1-week diet-washout and 2-weeks drug-washout interval. The participants (n=16) are randomly assigned to either of 7 days of low sodium (50 mmol/day) or high sodium diet (300 mol) after hospitalization. After completion of 7-days of first period, all participants are discharge and recommended to eat usual diet. After 1-week of diet washout, all participants are hospitalized for second period. The compliance of diet is determined by measurement of 24-hour urine sodium excretion. The 24-hour urine sodium excretion should be \< 100 mmol/24-hour in the low sodium diet period and \> 200 mmol/24-hour in high sodium diet period. On the morning of 7th day of each period (high sodium or low sodium diet period), all participants receive 60 mg of fimasartan in the fasting state. Blood samples for pharmacokinetic and pharmacodynamic study are drawn for 24-hour. The detailed measures are as followings: 1. High- and low-sodium intake 1. One of high- or low sodium intake for 7 days during each period 2. Low sodium intake : 50 mmol/day by diet 3. High sodium intake: 50 mmol/day by diet + 250 mmol/day by salt tablets 2. 24 hour excreted amount of sodium in urine to determine the compliance for the high- and low-sodium intake 1. 24 hour excreted amount of sodium in urine for low sodium intake \< 100 mmol 2. 24 hour excreted amount of sodium in urine for high sodium intake \> 200 mmol 3. Vital signs a. Systolic and diastolic blood pressures and pulse rate in sitting position and body temperature 4. Blood chemistry and complete blood count 1. Measure at the morning of first day after overnight fasting 2. white blood cell count, red blood count, hemoglobin, hematocrit, platelet, Calcium, sodium, potassium, glucose, blood urea nitrogen, creatinine, uric acid, cholesterol, albumin, total bilirubin, AST, ALT, blood urea nitrogen 5. Urinalysis a. potential of hydrogen, protein, bilirubin, glucose, urobilinogen, ketone, nitrite, blood 6. Pharmacokinetic blood sampling a. Plasma samples for fimasartan concentration 7. Pharmacodynamic blood sampling 1. Plasma samples for renin activity 2. Serum samples for aldosterone concentration