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PHARMACOKINETICS AND SAFETY OF SINGLE INTRAVENOUS AND ORAL DOSES OF DOLASETRON MESYLATE IN HEALTHY WOMEN
Author(s) -
KEUNG ANTHER C. F.,
LANDRIAULT HÉLÈNE,
LEFEBVRE MARC,
GOSSARD DENIS,
DEMPSEY ELLEN E.,
JUNEAU MARTIN,
DIMMITT DAN,
CASTLES MARK,
ROBERTS LISA,
SPÉNARD JEAN
Publication year - 1997
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/(sici)1099-081x(199705)18:4<361::aid-bdd25>3.0.co;2-i
Subject(s) - medicine , pharmacokinetics , anesthesia , oral administration , active metabolite , dosing , pharmacology
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 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 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 74 156 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. ©1997 by John Wiley & Sons, Ltd.