TABLE 2

Mean intrinsic clearance of sirolimus depletion with and without cyclosporine (and inhibition percentage) in rCYP 3A4 and rCYP 3A5 and in two pools of human liver microsomes genotyped for the CYP 3A5*3 single nucleotide polymorphism

Results are expressed as the mean and both values (n = 2 experiments) for rP450 and mean ± S.D. for microsomes (n = 3 experiments).

CLint of Sirolimus Depletiona
Inhibition
Without Cyclosporine
With 0.62 μM Cyclosporine
%
rCYP 3A4 2.36 (2.82; 1.90) 1.29 (1.39; 1.19) 44 (51; 37)
rCYP 3A5 0.64 (0.49; 0.79) 0.62 (0.55; 0.67) 8 (0; 15)
Microsomes CYP 3A5*3/*3 1277 ± 63 562 ± 35 52 (56; 59)b
Microsomes CYP 3A5*1/*3
1265 ± 223
784 ± 166
32 (31; 49)b

  • ↵ a Units are μl/pmol P450/min for rP450 and μl/mg protein/min for microsomes.

  • ↵ b Median (minimum; maximum).