Pharmacokinetics and safety of single intravenous and oral doses of dolasetron mesylate in healthy women.

Twenty-four healthy women received 2.4mgkg -1 dolasetron mesylate (1.8mgkg -1 dolasetron base) by a 10min intravenous administration and by oral administration. Pharmacokinetics of dolasetron and of its active reduced metabolite MDL 74 156 were monitored for 48h in plasma. Urine was collected from 0 to 48 h, blood pressure and heart rate were measured at 0, 0.08, 1, 2, 12, 24, and 36 h, and ECGs were measured at 0, 0.08 (intravenous only), 1, 2, and 36h after dosing. Dolasetron was widely distributed and rapidly reduced (mean t 1/2 =0.23 h) to MDL 74 156 (mean t 1/2 = 8 .05 and 9.12 after intravenous and oral administration respectively). MDL 74156 was extensively distributed; between 27 (oral route) and 33% (intravenous route) was eliminated unchanged in urine. Safety assessment showed mild to moderate headache, dizziness, and hot flushes after the intravenous administration and headache, abdominal cramps or pain, and constipation after oral administration. Small and clinically non-significant changes in PR, QRS, and QT c intervals were observed. We conclude that there is no obvious difference in dolasetron pharmacokinetics between healthy women and men and that dolasetron can be used as safely in women as in men.