PHARMACOKINETICS AND SAFETY OF SINGLE INTRAVENOUS AND ORAL DOSES OF DOLASETRON MESYLATE IN HEALTHY WOMEN

Twenty-four healthy women received 2.4 mg kg(-1) dolasetron mesylate ( 1.8 mg kg(-1) dolasetron base) by a 10 min intravenous administration and by oral administration. Pharmacokinetics of dolasetron and of its active reduced metabolite MDL 74 156 were monitored for 48 h in plasma . Urine was collected from 0 to 48 h, blood pressure and heart rate we re 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 36 h after dosing. Dolasetro n 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 h after intravenous and oral administration respectively). MDL 74156 was extensively distributed; b etween 27 (oral route) and 33% (intravenous route) was eliminated unch anged in urine. Safety assessment showed mild to moderate headache, di zziness, and hot flushes after the intravenous administration and head ache, abdominal cramps or pain, and constipation after oral administra tion. Small and clinically non-significant changes in PR, QRS, and QT( c) intervals were observed. We conclude that there is no obvious diffe rence in dolasetron pharmacokinetics between healthy women and men and that dolasetron can be used as safely in women as in men. (C) 1997 by John Wiley & Sons, Ltd.