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Pharmacokinetic interaction in rabbits between a new anticonvulsant, DL-3-hydroxy-3-ethyl-3-phenylpropionamide, and phenytoin.

Authors
  • Medina, L
  • García, L
  • Pérez, R
  • Fernández, A
  • Jung, H
Type
Published Article
Journal
The Journal of pharmacy and pharmacology
Publication Date
Dec 01, 1998
Volume
50
Issue
12
Pages
1393–1396
Identifiers
PMID: 10052855
Source
Medline
License
Unknown

Abstract

The effect of phenytoin on the disposition of DL-3-hydroxy-3-ethyl-3-phenylpropionamide (HEPP) has been studied in New Zealand white rabbits. Plasma HEPP levels decreased when the drug was administered with phenytoin. The area under the plasma concentration-time curve was reduced by 56.49% (from 43.23+/-7.0 to 18.81+/-2.03 microg h mL(-1)), the elimination half-life was also significantly (P<0.01) reduced (from 2.68+/-0.35 to 1.04+/-0.07 h) and the clearance was increased (from 0.35 to 0.81 L h(-1) kg(-1)). In-vitro protein binding to bovine serum albumin (BSA) and plasma was evaluated by equilibrium dialysis. Plasma protein binding was low (between 33.69 and 37.43% at concentrations ranging from 6.25 to 100 microg mL(-1)). The compound binds preferentially to albumin with an association constant (Ka) of 3.81 x 10(3) M(-1) at 37 degrees C. The results suggest a pharmacokinetic interaction between phenytoin and HEPP, probably on the drug-metabolizing enzyme system in the liver.

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