Bioavailability and pharmacokinetics of phenytoin during pregnancy |
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Authors: | C M Lander M T Smith J B Chalk C de Wytt P Symoniw I Livingstone M J Eadie |
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Institution: | (1) Department of Medicine, University of Queensland, and Royal Women’s Hospital, Brisbane, Australia |
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Abstract: | Summary Five epileptic women needing to commence phenytoin therapy during pregnancy received a single intravenous and a single oral
dose of phenytoin several days apart before starting regular intake of the drug. Plasma phenytoin concentration — time data
were analysed by three different pharmacokinetic techniques. However assessed, the mean oral bioavailability of the drug proved
to be about 90% of the intravenous bioavailability. This finding makes it unlikely that impaired bioavailability accounts
for the increase in oral phenytoin dosage necessary in pregnancy to maintain plasma phenytoin concentrations at pre-pregnancy
values. Phenytoin clearance in the pregnant subjects was approximately double the published values for phenytoin clearance
in nonpregnant persons. This suggests that increased (metabolic) clearance accounts for the increased phenytoin dosage requirement
of pregnancy. |
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Keywords: | phenytoin epileptic women pharmacokinetics bioavailability pregnancy |
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