TABLE 2.
Caffeine pharmacokinetic parameters in hCYP1A1/1A2, Cyp1a KO, WT, and HRN mice Data are the mean ± S.D. (% mean of C57BL/6J ± %S.D.); n = 4.
| Mouse Line | Cmax | V/F(obs) | HL | AUCinf(obs) | CL/F(obs) |
|---|---|---|---|---|---|
| ng/ml | ml/kg | h | h*ng/ml | ml/h/kg | |
| C57BL/6J | 2383 ± 628 (100 ± 26) | 1253 ± 494 (100 ± 39) | 0.94 ± 0.25 (100 ± 27) | 5704 ± 1265 (100 ± 22) | 905 ± 170 (100 ± 19) |
| Cyp1a KO | 3991 ± 472** (167 ± 20) | 992 ± 188 (79 ± 15) | 2.39 ± 0.2*** (253 ± 22) | 17651 ± 2073**** (309 ± 36) | 286 ± 35*** (32 ± 4) |
| hCYP1A1/1A2 | 3082 ± 194 (129 ± 8) | 1111 ± 55 (89 ± 4) | 1.3 ± 0.33 (138 ± 35) | 8397 ± 1797* (147 ± 32) | 615 ± 121* (68 ± 13) |
| HRN | 3744 ± 794* (157 ± 33) | 1057 ± 82 (84 ± 7) | 8.4 ± 0.8**** (891 ± 85) | 57,271 ± 2583**** (1004 ± 45) | 87 ± 3.8**** (9.7 ± 0.42) |
AUCinf(obs), area under the curve from dosing time extrapolated to infinity from the last observed caffeine concentration; CL/F(obs), clearance calculated using AUCinf(obs); Cmax, maximum observed concentration; HL, terminal half-life; V/F(obs), volume of distribution calculated using AUCinf(obs).
*
Significantly different from C57BL/6J (unpaired t test; two-tailed P values; *P < 0.05; **P < 0.01; ***P < 0.001; ****P < 0.0001).