NCT02147704

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

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 27 (actual)
• Sponsor: DongGuk University · Academic / Other
• Sex: Male
• Age: 20 Years – 45 Years
• Healthy volunteers: Accepted

Summary

It has been known that the blood pressure lowering effect of angiotensin receptor antagonists (ARBs) and angiotensin converting enzyme (ACE) inhibitors is impaired in patients on high sodium intake. There was an enhanced blood pressure lowering effect of ACE inhibitor when sodium intake was restricted or diuretics were added. The reason is partially explained by sodium sensitivity or low rennin activity in high sodium intake. However, the exact mechanism of sodium intake dependency is not clearly understood. In a recent study, an ARB, candesartan was revealed to have sodium intake dependency, showing lower plasma concentration when subjects were on high sodium intake compared to on low sodium intake. However, plasma concentration of another ARB, valsartan and an ACE inhibitor ramipril was not changed depending on the sodium intake. The strongly suggested mechanism is the involvement of transporter P-glycoprotein (Pg-P). the function and expression of Pg-P are modified by genetic polymorphism of multidrug resistance 1 gene. Although the transport mechanism of Fimasartan from gut is not fully understood, it has been known that the multidrug resistance 1 is not involved. Thus, the pharmacokinetic and pharmacodynamic property of fimasartan is expected not to be affected by the status of sodium intake. The present study is designed to investigate whether the pharmacokinetic and pharmacodynamic property of fimasartan is changed depending on the sodium intake.

Detailed description

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

Conditions

• Hypertension

Interventions

Type	Name	Description
DIETARY_SUPPLEMENT	High-sodium diet	1. One of high- or low sodium intake for 7 days during each period 2. High sodium intake: 50 mmol/day by diet + 250 mmol/day by salt tablets
DIETARY_SUPPLEMENT	low-sodium diet	1. One of high- or low sodium intake for 7 days during each period 2. Low sodium intake : 50 mmol/day by diet

Timeline

• Start date: 2014-05-01
• Primary completion: 2014-07-01
• Completion: 2014-09-01
• First posted: 2014-05-28
• Last updated: 2016-07-01

Locations

1 site across 1 country: South Korea