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 LineCmaxV/F(obs)HLAUCinf(obs)CL/F(obs)
ng/mlml/kghh*ng/mlml/h/kg
C57BL/6J2383 ± 628 (100 ± 26)1253 ± 494 (100 ± 39)0.94 ± 0.25 (100 ± 27)5704 ± 1265 (100 ± 22)905 ± 170 (100 ± 19)
Cyp1a KO3991 ± 472** (167 ± 20)992 ± 188 (79 ± 15)2.39 ± 0.2*** (253 ± 22)17651 ± 2073**** (309 ± 36)286 ± 35*** (32 ± 4)
hCYP1A1/1A23082 ± 194 (129 ± 8)1111 ± 55 (89 ± 4)1.3 ± 0.33 (138 ± 35)8397 ± 1797* (147 ± 32)615 ± 121* (68 ± 13)
HRN3744 ± 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).