Effect of the removal of individual antiepileptic drugs on antipyrine kinetics, in patients taking polytherapy.
1. Antipyrine (AP) clearance, half-life and volume of distribution were determined in 52 patients, taking one or more antiepileptic drug (AED), before and 4 weeks after the complete removal of phenytoin (PHT, n = 20), carbamazepine (CBZ, n = 15) and sodium valproate (VPA, n = 17). 2. PHT removal was associated with a mean 13% fall in AP clearance and a mean 16% increase in AP half-life, in patients who were also taking CBZ with or without barbiturates. There was no significant difference between patients who did, and did not, take barbiturates, in addition to CBZ. 3. CBZ removal was associated with a mean 45% fall in AP clearance and a mean 69% increase in AP half-life, if there was no inducing AED comedication, but had no effect on AP clearance and half-life if PHT and/or barbiturates were also being taken. 4. Removal of VPA had no effect on AP clearance or half-life. 5. The removal of PHT, CBZ and VPA had no significant effect on AP volume of distribution. 6. PHT appears to be a more powerful inducer of hepatic enzyme activity, as measured by the AP test, than is CBZ.
Patsalos
P N
PN
Institute of Neurology, National Hospital for Nervous Diseases, Queen Square, London.
Duncan
J S
JS
Shorvon
S D
SD
D000293:Adolescent; D000328:Adult; D000368:Aged; D000927:Anticonvulsants / Q000008:administration & dosage*; D000983:Antipyrine / Q000493:pharmacokinetics*; D004359:Drug Therapy, Combination; D004790:Enzyme Induction / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D008137:Longitudinal Studies; D008875:Middle Aged; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D000927:Anticonvulsants; D000983:Antipyrine