Comparisons of the pharmacokinetics and tolerability of fixed-dose combinations of amlodipine besylate/losartan and amlodipine camsylate/losartan in healthy subjects: a randomized, open-label, single-dose, two-period, two-sequence crossover study

Figures & data

Table 1 Summary of the PK results of amlodipine and losartan for the test drug (6.94 mg amlodipine besylate [5 mg as amlodipine]/50 mg losartan potassium) and the reference drug (5 mg amlodipine camsylate/50 mg losartan potassium)

Variable	Test drug (n=45)	Reference drug (n=45)	GMR (90% CI)a
	Mean ± SD (min–max)	Mean ± SD (min–max)
Amlodipine
Tmaxb (h)	6.0 (4.0–8.0)	6.0 (4.0–8.0)
Cmax (μg/L)	3.0±0.7 (1.7–4.5)	3.1±0.6 (1.8–4.7)	0.98 (0.94–1.01)
AUC0–t (h⋅μg/L)	119.5±36.2 (57.3–226.4)	123.7±37.9 (59.1–244.2)	0.97 (0.93–1.01)
AUC0–∞ (h⋅μg/L)	137.8±50.0 (72.9–294.7)	141.1±52.7 (66.2–357.2)
t1/2 (h)	46.4±16.2	43.6±12.9
Losartan
Tmaxb (h)	1.0 (0.5–3.0)	1.0 (0.3–2.0)
Cmax (μg/L)	242.8±128.5 (36.9–641.9)	249.6±107.6 (101.6–542.8)	0.91 (0.81–1.02)
AUC0–t (h⋅μg/L)	430.8±137.8 (200.4–859.5)	409.7±133.0 (226.7–815.4)	1.05 (0.98–1.12)
AUC0–∞ (h⋅μg/L)	451.3±139.6 (217.7–882.4)	432.3±136.8 (243.9–885.7)
t1/2 (h)	1.8±0.4	1.9±0.6

Notes: All values are presented as arithmetic mean ± SD.

a GMR of the test drug to the reference drug.

b Median (min–max).

Abbreviations: PK, pharmacokinetic; SD, standard deviation; GMR, geometric mean ratio; CI, confidence interval; T_max, time to the peak concentration; C_max, maximum plasma concentration; AUC_0–t, area under the concentration curve from time zero to the last quantifiable time point; AUC_0–∞, area under the concentration time curve from time 0 to infinity; t_1/2, half-life.

Figure 1 Mean plasma concentration–time profiles of (A) amlodipine and (B) losartan after a single oral dose of the test drug (6.94 mg amlodipine besylate [5 mg as amlodipine]/50 mg losartan potassium) or the reference drug (5 mg amlodipine camsylate/50 mg losartan potassium).

Abbreviation: h, hours.

Figure 2 Individual comparisons of the (A) C_max of amlodipine, (B) the AUC_0–t of amlodipine, (C) the C_max of losartan, and (D) the AUC_0–t of losartan after a single oral dose of the test drug (6.94 mg amlodipine besylate [5 mg as amlodipine]/50 mg losartan potassium) or the reference drug (5 mg amlodipine camsylate/50 mg losartan potassium).

Abbreviations: h, hours; C_max, maximum plasma concentration; AUC_0–t, area under the concentration curve from time zero to the last quantifiable time point.

Table 2 AEs reported following a single oral dose of the test drug (6.94 mg amlodipine besylate [5 mg as amlodipine]/50 mg losartan potassium) or the reference drug (5 mg amlodipine camsylate/50 mg losartan potassium)

	Treatment		P-value
	Test drug (n=46)	Reference drug (n=45)
Number (%) of subjects with at least one AE	11 (23.9)	15 (33.3)	0.360a
Number of AEs	23	23	1.000b
Number (%) of subjects with at least one drug-related AE	5 (10.9)	11 (24.4)	0.210a
Number of drug-related AEs	11	16	0.441a

Notes:

a Chi-square test.

b Fisher’s exact test.

Abbreviation: AE, adverse event.

Figure 3 Mean (A) SBP, (B) DBP, and (C) PR after a single oral administration of the test drug (6.94 mg amlodipine besylate [5 mg as amlodipine]/50 mg losartan potassium) or the reference drug (5 mg amlodipine camsylate/50 mg losartan potassium).

Abbreviations: SBP, systolic blood pressure; h, hours; DBP, diastolic blood pressure; PR, pulse rate.