A comparative study of the effect of carbamazepine and valproic acid on the pharmacokinetics and metabolic profile of topiramate at steady state in patients with epilepsy.
Epilepsia
; 46(7): 1046-54, 2005 Jul.
Article
en En
| MEDLINE
| ID: mdl-16026556
ABSTRACT
PURPOSE:
To compare the influence of enzyme-inducing comedication and valproic acid (VPA) on topiramate (TPM) pharmacokinetics and metabolism at steady state.METHODS:
Three groups were assessed (a) patients receiving TPM mostly alone (control group, n =13); (b) patients receiving TPM with carbamazepine (CBZ; n = 13); and (c) patients receiving TPM with VPA (n = 12). TPM and its metabolites were assayed in plasma and urine by liquid chromatography-mass spectrometry (LC-MS).RESULTS:
No significant differences were found in TPM oral (CL/F) and renal (CL(r)) clearance between the VPA group and the control group. Mean TPM CL/F and CL(r) were higher in the CBZ group than in controls (2.1 vs. 1.2 L/h and 1.1 vs. 0.6L/h, respectively; p < 0.05). In all groups, the urinary recovery of unchanged TPM was extensive and accounted for 42-52% of the dose (p > 0.05). Urinary recovery of 2,3-O-des-isopropylidene-TPM (2,3-diol-TPM) accounted for 3.5% of the dose in controls, 2.2% in the VPA group (p > 0.05), and 13% in the CBZ group (p < 0.05). The recovery of 10-hydroxy-TPM (10-OH-TPM) was twofold higher in the CBZ group than in controls, but it accounted for only <2% of the dose. The plasma concentrations of TPM metabolites were severalfold lower than those of the parent drug.CONCLUSIONS:
Renal excretion remains a major route of TPM elimination, even in the presence of enzyme induction. The twofold increase in TPM-CL/F in patients taking CBZ can be ascribed, at least in part, to stimulation of the oxidative pathways leading to formation of 2,3-diol-TPM and 10-OH-TPM. VPA was not found to have any clinically significant influence on TPM pharmacokinetic and metabolic profiles.
Buscar en Google
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Carbamazepina
/
Ácido Valproico
/
Epilepsia
/
Fructosa
/
Anticonvulsivantes
Límite:
Adult
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Epilepsia
Año:
2005
Tipo del documento:
Article
País de afiliación:
Israel