title: Pharmacokinetics and safety of single intravenous and oral doses of dolasetron mesylate in healthy women.
abstract: 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 74156 were monitored for 48 h 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 36 h after dosing. Dolasetron was widely distributed and rapidly reduced (mean t1/2 = 0.23 h) to MDL 74156 (mean t1/2 = 8.05 and 9.12 h 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 QTc 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.
authors.affiliation: Hoechst Marion Roussel, Kansas City, MO 64134-0627, USA.
authors.forename: A C
authors.initials: AC
authors.lastname: Keung
authors.forename: H
authors.initials: H
authors.lastname: Landriault
authors.forename: M
authors.initials: M
authors.lastname: Lefebvre
authors.forename: D
authors.initials: D
authors.lastname: Gossard
authors.forename: E E
authors.initials: EE
authors.lastname: Dempsey
authors.forename: M
authors.initials: M
authors.lastname: Juneau
authors.forename: D
authors.initials: D
authors.lastname: Dimmitt
authors.forename: M
authors.initials: M
authors.lastname: Castles
authors.forename: L
authors.initials: L
authors.lastname: Roberts
authors.forename: J
authors.initials: J
authors.lastname: Spenard
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000932:Antiemetics / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D005260:Female; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D011807:Quinolizines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics*; D012737:Sex Factors
chemical_list: D000932:Antiemetics; D007211:Indoles; D011807:Quinolizines; D012702:Serotonin Antagonists; C060344:dolasetron