Comparative pharmacokinetics of a fixed-dose combination vs concomitant administration of telmisartan and S-amlodipine in healthy adult volunteers

Figures & data

Table 1 Baseline characteristics of study subjects (n=68)

Variables	Values
SBP	129.59±7.72 (102–138)
DBP	81.18±4.87 (70–89)
Creatinine	0.94±0.10 (0.74–1.26)
GOT	20.41±4.52 (14–33)
GPT	20.71±8.90 (10–47)

Note: Data are expressed as mean ± standard deviation (min–max).

Abbreviations: SBP, systolic blood pressure; DBP, diastolic blood pressure; GOT, glutamin oxalacetic transaminase; GPT, glutamic pyruvate transaminase.

Figure 1 Disposition of volunteers.

Abbreviations: AE, adverse event; RT, reference-test; TR, test-reference.

Figure 2 Mean (standard deviation) plasma concentration profiles of telmisartan after administration of FDC tablet (40 mg telmisartan/5 mg S-amlodipine) and coadministration of 40 mg telmisartan with 5 mg S-amlodipine in healthy male subjects.

Notes: Linear scale (A); Iog scale (B).

Abbreviation: FDC, fixed-dose combination.

Figure 3 Mean (standard deviation) plasma concentration profile of S-amlodipine after administration of FDC tablet (40 mg telmisartan/5 mg S-amlodipine) and coadministration of 40 mg telmisartan with 5 mg S-amlodipine in healthy male subjects.

Notes: Linear scale (A); log scale (B).
Abbreviation: FDC, fixed-dose combination.

Table 2 PK properties of telmisartan and S-amlodipine following administration of an FDC tablet containing 40 mg telmisartan and 5 mg S-amlodipine or coadministration of 40 mg telmisartan with 5 mg S-amlodipine in healthy male subjects (n=57)

Ingredient	PK parameter	FDC	Coadministration
Telmisartan	Cmax (ng/mL)	122.13±64.55	138.52±65.45
	AUCt (ng·h/mL)	1,225.73±749.80	1,268.76±740.52
	AUCinf (ng·h/mL)	1,416.01±944.13	1,448.59±888.73
	t1/2 (h)	17.17±6.21	17.73±5.43
	Tmax (h)a	2.0 (0.50~4.00)	1.5 (0.25~4.00)
S-amlodipine	Cmax (ng/mL)	2.83±0.58	2.83±0.71
	AUCt (ng·h/mL)	145.57±37.37	141.46±36.79
	AUCinf (ng·h/mL)	159.08±46.60	154.28±45.37
	t1/2 (h)	44.20±8.62	43.85±9.67
	Tmax (h)a	5.00 (4.00~10.00)	5.00 (3.00~8.00)

Notes: Data are expressed as mean ± standard deviation;

a values expressed as median (range).

Abbreviations: PK, pharmacokinetic; FDC, fixed-dose combination; C_max, maximum plasma concentration; T_max, time to reach C_max; AUC_inf, area under the plasma concentration–time curve from time zero to infinity; AUC_t, area under the curve from time zero to the last sampling time; t_1/2, terminal elimination half-life.

Table 3 Geometric mean ratios (90% CI) of the PK properties of telmisartan and S-amlodipine following administration of an FDC tablet containing 40 mg telmisartan and 5 mg S-amlodipine or coadministration of 40 mg telmisartan with 5 mg S-amlodipine in healthy male subjects (n=57)

Ingredient	PK parameter	Geometric mean ratio (90% CI)	Intra-individual CV (%)
Telmisartan	Cmax (ng/mL)	0.8782 (0.8167–0.9444)	23.17
	AUCt (ng·h/mL)	0.9662 (0.9210–1.0136)	15.28
S-amlodipine	Cmax (ng/mL)	1.0069 (0.9723–1.0427)	11.16
	AUCt (ng·h/mL)	1.0324 (0.9969–1.0690)	11.14

Abbreviations: PK, pharmacokinetic; FDC, fixed-dose combination; CV, coefficient of variation; C_max, maximum plasma concentration; AUC_t, area under the curve from time zero to the last sampling time.

Figure 4 Mean (standard deviation) SBP and DBP after administration of FDC tablet (40 mg telmisartan/5 mg S-amlodipine) and coadministration of 40 mg telmisartan with 5 mg S-amlodipine in healthy male subjects.

Notes: SBP (A); DBP (B).
Abbreviations: SBP, systolic blood pressure; DBP, diastolic blood pressure; FDC, fixed-dose combination.