The influence of dietary sodium content on the pharmacokinetics and pharmacodynamics of fimasartan

Figures & data

Table 1 Urinary excreted amount of electrolyte, plasma renin activity, plasma aldosterone concentration, and blood pressure during the low sodium diet and high sodium diet periods (n=16)

Variables	Low sodium diet		High sodium diet
	Baseline (day 6)	Fimasartan (day 7)	Baseline (day 6)	Fimasartan (day 7)
Urinary excreted amount of electrolyte (mEq/day)
24-hour sodium	59.9±18.6	67.0±19.4	283.2±49.4	252.4±59.5
24-hour potassium	46.6±8.5	43.6±12.4	50.3±8.9	41.2±7.1
Serum aldosterone concentration (mg/dL)
Before dose	19.3±13.3	16.7±6.0	5.2±3.0	4.5±2.5
4 hours after dose	18.2±7.7	6.4±2.8	3.7±1.9	1.5±1.2
24 hours after dose	16.7±6.0	14.4±5.6	4.5±2.5	2.5±1.5
AUC0–24 h	353.7±97.3	209.0±53.2	71.6±32.2	46.0±26.4
Plasma renin activity (ng/mL/h)
Before dose	7.9±3.4	5.8±3.0	2.1±1.8	1.6±1.3
4 hours after dose	5.9±3.4	23.2±2.9	1.2±1.1	8.3±6.8
24 hours after dose	5.8±3.0	21.2±3.6	1.6±1.3	9.1±8.1
AUC0–24 h	138.7±59.4	536.7±65.5	38.0±44.9	187.2±142.6
Systolic blood pressure (mmHg)
Before dose	118.1±14.1	116.9±8.0	117.7±9.4	118.4±9.3
4 hours after dose	–	107.1±11.3	–	112.2±11.0
24 hours after dose	–	109.3±11.8	–	111.0±7.8
Diastolic blood pressure (mmHg)
Before dose	73.9±7.5	75.8±5.4	70.8±7.6	74.4±8.4
4 hours after dose	–	63.9±6.2	–	67.5±7.5
24 hours after dose	–	68.8±7.8	–	68.4±5.4

Notes: All variables are represented as mean ± standard deviation. –, represents no data available.

Abbreviation: AUC_{0–24 h}, area under the curve from before dose to 24 hours after dose.

Table 2 Summary of pharmacokinetic parameters of fimasartan during the low sodium diet and high sodium diet periods (n=16)

PK Variables	Low sodium diet	High sodium diet
Tmax (h)	2.7±2.2	2.3±2.1
Cmax (μg/L)	119.0±102.2	94.0±70.5
AUC0–24 h (μg*h/L)	444.3±150.4	410.8±165.8
AUC0–∞ (μg*h/L)	465.7±152.0	429.1±170.4
T1/2 (h)	5.9±1.1	5.7±0.8

Note: All variables are represented as mean ± standard deviation.

Abbreviations: AUC_{0–24 h}, area under the curve from before dose to 24 hours after dose; C_max, maximal plasma concentration; T_1/2, terminal elimination half-life; T_max, time to C_max.

Figure 1 Mean plasma concentration–time curves of fimasartan during the low sodium diet and high sodium diet periods.

Figure 2 Comparison of individual systemic exposure of fimasartan during the low sodium diet and high sodium diet periods.

Abbreviation: AUC_{0–24 h}, area under the curve from before dose to 24 hours after dose.

Figure 3 Comparison of baseline area under the curve from before dose to 24 hours after dose (AUC_{0–24 h}) versus treatment AUC_{0–24 h}.

Notes: (A) Comparison of baseline area under the curve from before dose to 24 hours after dose (AUC_{0–24 h}) versus treatment AUC_{0–24 h} of serum aldosterone concentration (SAC). (Closed circle, low sodium diet; open circle, high sodium diet; blue lines, linear regression line and its 95% confidence intervals; and black dot line, line of identity.) (B) Comparison of baseline AUC_{0–24 h} versus treatment AUC_{0–24 h} of plasma renin activity (PRA). (Closed circle, low sodium diet; open circle, high sodium diet; black solid line, hyperbolic regression line; and black dot line, line of identity.)