Effect of vigabatrin on the pharmacokinetics of carbamazepine

J Clin Pharm Ther. 2002 Dec;27(6):427-30. doi: 10.1046/j.1365-2710.2002.00441.x.

Abstract

Objective: To evaluate a possible interaction between vigabatrin and carbamazepine in epileptic patients.

Methods: Steady-state serum concentrations of carbamazepine with and without vigabatrin were compared. The study group consisted of 15 patients (eight females, seven males, and mean age 31 +/- 12 years), with refractory partial epilepsy. They received vigabatrin as add-on therapy. Patients received carbamazepine monotherapy for at least 6 months and the carbamazepine-vigabatrin combination for at least 3 months. Blood samples were obtained in the morning, before the first daily dose and the carbamazepine plasma concentrations were analysed by fluorescence polarization immunoassay (TDx System).

Results: No statistically significant differences were found in mean carbamazepine daily dose. Mean trough concentrations were 7.9 +/- 1.4 microg/mL with carbamazepine alone, and 6.5 +/- 2.0 microg/mL with carbamazepine-vigabatrin association (P < 0.03). The mean values of pharmacokinetic parameters were: level/dose ratio (L/D) = 0.59 +/- 0.20 vs. 0.45 +/- 0.15 (P < 0.05) and plasma clearance (Cl) = 78.5 +/- 25.8 vs. 105.8 +/- 38.9 mL/h/kg (P < 0.05), with carbamazepine alone and carbamazepine-vigabatrin combination, respectively.

Conclusion: Vigabatrin produced a statistically significant increase in the plasma clearance of carbamazepine when the two drugs were given simultaneously.

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / blood
  • Anticonvulsants / pharmacokinetics*
  • Anticonvulsants / therapeutic use
  • Carbamazepine / administration & dosage
  • Carbamazepine / blood
  • Carbamazepine / pharmacokinetics*
  • Carbamazepine / therapeutic use
  • Drug Interactions
  • Drug Therapy, Combination
  • Epilepsy / drug therapy
  • Female
  • Humans
  • Male
  • Middle Aged
  • Vigabatrin / administration & dosage
  • Vigabatrin / pharmacology*
  • Vigabatrin / therapeutic use

Substances

  • Anticonvulsants
  • Carbamazepine
  • Vigabatrin