Pharmacokinetics and relative bioavailability of fixed-dose combination of clopidogrel and aspirin versus coadministration of individual formulations in healthy Korean men

Figures & data

Table 1 Demographics of study subjects

Variables	Values
Age (yrs)	25.53±2.87 (21–38)
Weight (kg)	69.95±7.72 (50.3–87.5)
PT (s)	10.85±0.41 (10.10–11.90)
aPTT (s)	33.21±3.14 (27.20–40.30)
BT (s)	89.43±24.61 (60–150)

Note: Mean ± SD (range).

Abbreviations: aPTT, activated partial thromboplastin time; BT, bleeding time; PT, prothrombin time; SD, standard deviation.

Table 2 Pharmacokinetic parameters of clopidogrel, aspirin, and salicylic acid after single-dose oral administration of FDC capsules or coadministration of individual formulations of clopidogrel 75 mg/aspirin 100 mg (n=53)

Parameter	FDC	Coadministration
Clopidogrel
AUClast, ng·h/mL	6.41±7.70	5.95±6.42
AUCinf, ng·h/mL	6.57±7.75	6.46±6.95
Cmax, ng/mL	3.89±3.82	3.73±4.81
Tmax, ha	0.67 (0.33–2.00)	0.67 (0.33–3.00)
t1/2, h	5.21±4.35	6.31±6.54
Tlast, ha	12.00 (3.00–24.00)	12.00 (4.00–24.00)
Aspirin
AUClast, ng·h/mL	1,777.27±452.17	1,822.41±510.13
AUCinf, ng·h/mL	1,986.54±464.54	2,000.69±695.24
Cmax, ng/mL	783.58±281.68	870.60±386.48
Tmax, ha	4.00 (2.00–6.00)	4.00 (2.00–6.00)
t1/2, h	0.63±0.36	0.65±0.36
Tlast, ha	6.00 (5.00–10.00)	6.00 (5.00–10.00)
Salicylic acid
AUClast, ng·h/mL	47,219.97±13,384.12	46,523.63±13,398.18
AUCinf, ng·h/mL	51,138.82±13,715.45	49,788.69±13,335.69
Cmax, ng/mL	8,620.57±1,715.92	8,512.83±1,687.48
Tmax, ha	5.00 (3.50–6.00)	5.00 (3.00–6.00)
t1/2, h	2.23±0.44	2.15±0.38
Tlast, ha	12.00 (12.00–24.00)	12.00 (12.00–24.00)

Note: Mean ± SD,

a values expressed as median (range).

Abbreviations: FDC, fixed-dose combination; CV, coefficient of variance; SD, standard deviation; AUC_0–t, area under the plasma concentration–time curve from time zero to last observation; AUC_inf, area under the plasma concentration–time curve from time zero to infinity; C_max, peak concentration of the drug; T_last, time of the last quantifiable concentration; T_max, time needed to achieve C_max; t_1/2, elimination half-life.

Table 3 Statistical comparison of clopidogrel, aspirin, and salicylic acid after single-dose oral administration of FDC capsules or coadministration of individual formulations of clopidogrel 75 mg/aspirin 100 mg (n=53)

Parameters	Geometric mean ratio (90% CI)	Intraindividual CV (%)
Clopidogrel
Cmax	1.0816 (0.9507, 1.2305)	41.24
AUClast	0.9771 (0.8427, 1.1329)	47.91
AUCinf	0.9418 (0.8057, 1.1009)	50.85
Aspirin
Cmax	0.9265 (0.8358, 1.0269)	32.44
AUClast	0.9825 (0.9265, 1.0418)	18.16
AUCinf	1.0123 (0.9124, 1.1232)	32.76
Salicylic acid
Cmax	1.0108 (0.9681, 1.0555)	13.34
AUClast	1.0128 (0.9794, 1.0472)	10.31
AUCinf	1.0237 (0.9952, 1.0531)	8.70

Note: Bioequivalence criteria are defined as 90% CI of the geometric mean ratios of T/R of between 0.80 and 1.25 for C_max, AUC_last, and AUC_inf.

Abbreviations: FDC, fixed-dose combination; CI, confidence interval; CV, coefficient of variance; AUC_inf, area under the plasma concentration–time curve from time zero to infinity; C_max, peak concentration of the drug; T/R, test/reference.

Figure 1 Mean plasma concentration versus time profiles.

Note: Linear scale (A) and log scale (B) of mean plasma concentration versus time profiles of clopidogrel, aspirin and salicylic acid in healthy subjects (n=53) after single-dose oral administration of two capsules of fixed-dose combination as test (open circle) and coadministration of two tablets of clopidogrel 75 mg and two capsules of aspirin 100 mg as reference (closed circle).