FT103 | FT105 | FT110 | FT112 | FT113 | FT127 | Mean ± S.D. | |
---|---|---|---|---|---|---|---|
CYP3A4 protein1-a | |||||||
UT | 8.8 | und | und | und | und | und | 1.5 ± 3.6 |
RIF | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
ELT5 | N.D. | N.D. | N.D. | N.D. | und | und | und |
ELT25 | N.D. | 34 | und | 53 | und | 10 | 19.3 ± 23.31-150 |
ELT50 | 76 | 32 | und | 100 | und | 12 | 36.9 ± 42.41-150 |
CYP3A4 mRNA1-a | |||||||
UT | N.D. | N.D. | 28 | und | 19 | N.D. | 23 ± 10.0 |
RIF | N.D. | N.D. | 100 | 100 | 100 | N.D. | 100 |
ELT5 | N.D. | N.D. | N.D. | N.D. | 25 | N.D. | 25.2 |
ELT25 | N.D. | N.D. | 100 | 65 | 82 | N.D. | 82.4 ± 17.51-160 |
ELT50 | N.D. | N.D. | 127 | 62 | 104 | N.D. | 97.9 ± 32.71-160 |
CSAO1-a | |||||||
UT | 5.8 | 19 | 46 | und | 20 | 20 | 18.4 ± 15.8 |
RIF | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
ELT5 | N.D. | N.D. | N.D. | N.D. | 2.0 | 16 | 8.9 ± 9.8 |
ELT25 | N.D. | 25 | 25 | 46 | 11 | 25 | 26.2 ± 12.41-165 |
ELT50 | 19 | 50 | 10 | 71 | 20 | 28 | 33.0 ± 22.91-165 |
N.D., not determined; und, below level of detection.
↵1-a Relative levels of CYP3A4 protein and mRNA and rates of cyclosporine A oxidation (CSAO) in untreated cells (UT) or in cells treated with 5, 25, or 50 μM eletriptan (ELT), with respect to the corresponding data in RIF-treated cells (arbitrarily taken as 100).
↵1-150 Levels of CYP3A4 protein: in ELT25- and ELT50-treated cells, significantly lower than in RIF-treated cells, P = .0015 and .015, respectively, and in untreated cells, significantly lower than in RIF-treated cells, P < .0001.
↵1-160 Levels of CYP3A4 mRNA: in ELT25- and ELT50-treated cells, significantly greater than in untreated cells, P = .0006 and .01, respectively, and in RIF-treated cells, significantly greater than in untreated cells, P = .02.
↵1-165 Rates of cyclosporine A oxidation: in ELT25- and ELT50-treated cells, significantly lower than in RIF-treated cells, P = .0002 and .0008, respectively, and in untreated cells, significantly lower than in RIF-treated cells, P < .0001. For absolute rates of cyclosporine A oxidation, see Fig.2.