Table 2.
Drug-drug interactions of gefitinib (Gef) with/without losartan (Los) and SSRIs: fluoxetine (Flx), citalopram (Cit), fluvoxamine (Flu), paroxetine (Par), sertraline (Ser), and venlafaxine (Ven). (A) Gefitinib, (B) losartan, and (C) SSRIs results. Hepatocytes were incubated with the respective drugs, and then the amount remaining of the drugs (in relation to the amount measured at 0 h) were determined after 3 h. The assays were performed with duplicate injection, and the results reported as mean ± SD. Welch's T-test was performed to determine two-tailed unadjusted p-values for statistical significance. Results showing statistical significance (p-value < 0.05) when compared to the drug alone.
| (A) Gefitinib (Gef) |
(B) Losartan (Los) |
(C) SSRIs |
||||
|---|---|---|---|---|---|---|
| Components | (%) | P-Value | (%) | P-Value | (%) | P-Value |
| Alone (Gef, Los, Flx) | 66 ± 7 | – | 85 ± 2 | – | 30 ± 2 | – |
| Gef + Los | 64 ± 9 | 0.829 | 88 ± 13 | 0.790 | ||
| Gef + Flx | 70 ± 0 | 0.496 | 35 ± 1 | 0.123 | ||
| Gef + Los + Flx | 119 ± 0 | 0.009 | 96 ± 1 | 0.026 | 95 ± 5 | 0.003 |
| Alone (Cit) | – | – | – | – | 64 ± 2 | – |
| Gef + Cit | 85 ± 1 | 0.065 | – | – | 68 ± 1 | 0.117 |
| Gef + Los + Cit | 77 ± 9 | 0.280 | 77 ± 4 | 0.131 | 69 ± 5 | 0.305 |
| Alone (Flu) | – | – | – | – | 40 ± 1 | – |
| Gef + Flu | 66 ± 7 | 0.995 | – | – | 49 ± 6 | 0.162 |
| Gef + Los + Flu | 130 ± 13 | 0.027 | 103 ± 14 | 0.229 | 77 ± 8 | 0.022 |
| Alone (Par) | – | – | – | – | 59 ± 1 | – |
| Gef + Par | 91 ± 3 | 0.042 | – | – | 64 ± 2 | 0.065 |
| Gef + Los + Par | 90 ± 3 | 0.048 | 86 ± 6 | 0.859 | 65 ± 2 | 0.046 |
| Alone (Ser) | – | – | – | – | 13 ± 1 | – |
| Gef + Ser | 106 ± 5 | 0.025 | – | – | 40 ± 4 | 0.009 |
| Gef + Los + Ser | 92 ± 0 | 0.037 | 110 ± 2 | 0.008 | 32 ± 2 | 0.008 |
| Alone (Ven) | – | – | – | – | 65 ± 2 | – |
| Gef + Ven | 68 ± 5 | 0.717 | – | – | 81 ± 7 | 0.093 |
| Gef + Los + Ven | 83 ± 3 | 0.090 | 89 ± 2 | 0.232 | 94 ± 17 | 0.141 |