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Interaction between Ketoconazole and Almotriptan in Healthy Volunteers

2003; Wiley; Volume: 43; Issue: 4 Linguagem: Inglês

10.1177/0091270003252242

1552-4604

Joseph C. Fleishaker, Beth D. Herman, Barbara J. Carel, Nkechi Azie,

Blood Pressure and Hypertension Studies

The interaction between almotriptan, a 5‐HT 1B/1D agonist, and the potent CYP3A4 inhibitor ketoconazole was examined in 16 healthy volunteers. Subjects received (A) 12.5 mg almotriptan orally on Day 2 of a 3‐day regimen of 400 mg ketoconazole once daily and (B) 12.5 mg almotriptan in a crossover design. Plasma and urine concentrations of almotriptan were measured by HPLC. Treatment effects on almotriptan pharmacokinetics were assessed by analysis of variance. Ketoconazole coadministration increased mean almotriptan AUC and C max from 312 to 490 ng h/mL and 52.6 to 84.5 ng/mL, respectively. Mean oral clearance was decreased from 40.7 to 26.2 L/h by ketoconazole, with an accompanying increase in the fraction of almotriptan excreted unchanged in the urine (40.6% to 53.3%) and a decrease in renal clearance (16.4 to 13.8 L/h). These effects were statistically significant. The effects of ketoconazole on almotriptan clearance were consistent with inhibition of the CYP3A4‐mediated metabolism and a slight effect on the active tubular secretion of almotriptan.