TABLE 3

Systemic exposure (AUC) of triazolam and 1′-OH triazolam after oral triazolam administration (0.5 mg/kg) and oral coadministration of gefitinib (25 mg/kg) or ketoconazole (35 mg/kg) to mice

VehicleGefitinibKetoconazole
Triazolam
    Cyp3a(−/−)317 ± 62294 ± 21374 ± 50
    Cyp3a(−/−)Tg-3A4Hep370 ± 49248 ± 14*588 ± 68**††
    Cyp3a(−/−)Tg-3A4Int140 ± 15**132 ± 23**458 ± 44*†††
    Cyp3a(−/−)Tg-3A4Hep/Int130 ± 19**77 ± 15***549 ± 38**†††
    Wild-type194 ± 23*N.D.467 ± 43*†††
1′-OH Triazolam
    Cyp3a(−/−)165 ± 34145 ± 13186 ± 19
    Cyp3a(−/−)Tg-3A4Hep304 ± 19**193 ± 5697 ± 13**†††
    Cyp3a(−/−)Tg-3A4Int211 ± 27235 ± 35*144 ± 23*
    Cyp3a(−/−)Tg-3A4Hep/Int261 ± 40*202 ± 45150 ± 22
    Wild-type237 ± 29N.D.144 ± 14*††
  • AUC0–320 min (h · μg/l), area under plasma concentration-time curve up to 320 min. Data are presented as means ± S.D., n = 4–5.

  • * P < 0.05,

  • ** P < 0.01, and

  • *** P < 0.001 compared with Cyp3a(−/−) mice;

  • P < 0.05,

  • †† P < 0.01, and

  • ††† P < 0.001 compared with untreated strain.

  • N.D., not determined.