Table 3.
Mean (s.d.) pharmacokinetic parameters for simvastatin and β-hydroxysimvastatin on day 14 (Study 1).
| Parameter | SIM 10 mg+EZE 0.25 mg (n = 11) | SIM 10 mg+EZE 1 mg (n = 12) | SIM 10 mg+EZE 10 mg (n = 11) | SIM 10 mg (n = 12) |
|---|---|---|---|---|
| Simvastatin | ||||
| Cmax (ng ml−1) | 2.94 (1.84) | 2.38 (1.32) | 2.65 (1.65) | 2.36 (1.09) |
| tmaxa (h) | 1 (0.5–2) | 1 (0.5–2) | 1 (0.5-2) | 1 (0.5-3) |
| AUC(0,24 h) (ng ml−1 h) | 8.07 (4.67) | 7.82 (6.15) | 8.42 (7.02) | 6.82 (3.29) |
| t1/2 (h) | 3.76b (1.85) | 2.78c (1.98) | 3.46b (2.11) | 3.52c (3.06) |
| CL/F (kg−1) (ml min−1 kg−1) | 362 (172) | 455 (262) | 502 (509) | 448 (283) |
| Vd/F (kg−1) (l kg−1) | 111b (94) | 85.4c (44) | 112b (76) | 116c (109) |
| β-Hydroxysimvastatin | ||||
| Cmax (ng ml−1) | 0.90 (1.03) | 0.63 (0.34) | 0.62 (42) | 0.57 (0.26) |
| tmaxa (h) | 3 (1–8) | 3.5 (0.5–8) | 3 (0.5–6) | 4 (1–8) |
| AUC(0,24 h) (ng ml−1 h) | 9.10 (11.72) | 5.64 (4.85) | 5.55 (3.95) | 5.10 (2.63) |
| t1/2 (h) | 6.20d (4.80) | 5.15d (1.88) | 4.69e (1.64) | 4.91d (2.00) |
s.d., standard deviation; SIM, simvastatin; EZE, ezetimibe; Cmax, maximum plasma concentration; tmax, time to reach Cmax; AUC, area under the plasma concentration-time curve; t1/2, terminal half-life associated with the terminal slope of the semilogarithmic plasma concentration-time curve; CL/F, apparent oral clearance where F represents bioavailability and CL represents total clearance; Vd, volume of distribution.
a
Median (range).
b
n = 10,
c
n = 11,
d
n = 8,
e
n = 7.