TABLE 4.
Rifampin pharmacokinetic parameters among subjects with SLCO1B1 c.463C>A and c.521T>C SNPs in univariate analyses
| Parameter (no. of subjects)e | Arithmetic mean (± SD) | Geometric mean | RGM | P valueb |
|---|---|---|---|---|
| SLCO1B1 c.463C>Aa | ||||
| AUC0-24 | ||||
| All (86) | 46.0 (23.9) | 40.3 | ||
| CC (71) | 49.4 (24.0) | 44.4 | 0.58 | 0.0002 |
| CA (15) | 29.9 (16.6) | 25.6 | ||
| Cmax | ||||
| All (88) | 8.4 (4.8) | 7.0 | ||
| CC (73) | 8.8 (4.8) | 7.5 | 0.66 | 0.03 |
| CA (15) | 6.3 (4.5) | 5.0 | ||
| Clss/F | ||||
| All (86) | 17.0 (10.4) | 14.7 | ||
| CC (71) | 15.1 (7.9) | 13.5 | 1.63 | 0.0009 |
| CA (15) | 26.1 (15.7) | 22.0 | ||
| Vz/F | ||||
| All (86) | 57.2 (59.4) | 45.0 | ||
| CC (71) | 47.1 (30.0) | 41.0 | 1.71 | 0.0004 |
| CA (15) | 104.8 (118.1) | 70.1 | ||
| Half-life | ||||
| All (86) | 2.3 (1.1) | 2.1 | ||
| CC (71) | 2.2 (0.8) | 2.1 | 1.05 | 0.74 |
| CA (15) | 2.6 (2.1) | 2.2 | ||
| SLCO1B1 c.521T>Cc | ||||
| AUC0-24 | ||||
| TT (73) | 43.8 (22.6) | 38.5 | 1.37 | 0.11d |
| TC (11) | 56.3 (30.5) | 50.2 | ||
| CC (2) | 68.1 (15.6) | 67.2 | ||
| Cmax | ||||
| TT (74) | 8.4 (5.0) | 7.0 | 1.04 | 0.92d |
| TC (11) | 8.3 (3.3) | 7.4 | ||
| CC (3) | 9.5 (6.8) | 6.7 | ||
| Clss/F | ||||
| TT (73) | 17.8 (10.9) | 15.4 | 0.74 | 0.14d |
| TC (11) | 13.2 (5.6) | 11.9 | ||
| CC (2) | 9.1 (2.1) | 8.9 | ||
| Vz/F | ||||
| TT (73) | 57.6 (62.7) | 44.4 | 1.09 | 0.89d |
| TC (11) | 58.5 (39.2) | 50.9 | ||
| CC (2) | 37.0 (4.5) | 36.9 | ||
| Half-life | ||||
| TT (73) | 2.1 (1.0) | 2.0 | 1.47 | <0.001d |
| TC (11) | 3.3 (1.5) | 3.0 | ||
| CC (2) | 2.9 (0.3) | 2.9 |
a
The ratio of geometric means (RGM) for SLCO1B1 c.463C>A genotypes was calculated with CA/CC.
b
P values obtained by t testing of an unpaired ln-transformed variable for the SLCO1B1 c.463CC genotype versus the c.463CA genotype.
c
The RGM of SLCO1B1 c.521 was calculated with (TC + CC)/TT.
d
P values obtained by ANCOVA of a ln-transformed variable.
e
Clss/F, apparent oral plasma clearance at steady state; Vz/F, apparent volume of distribution based on the terminal phase.