Steady state pharmacokinetics of carbamazepine-phenobarbital interaction in patients with epilepsy.

Two carbamazepine (CBZ) tablet formulations (conventional, CBZ-CO, or controlled release, CBZ-CR) are commonly prescribed in monotherapy or in comedication with phenobarbital (PB) in the treatment of epilepsies. This study compares the pharmacokinetics of CBZ-CO against CBZ-CR in patients with epilepsies chronically treated with CBZ in monotherapy or CBZ-PB in bitherapy, the effect of PB on CBZ-CO and CBZ-CR pharmacokinetic parameters, and the effect of the two formulations of CBZ on PB pharmacokinetic parameters. The absorption rate constant (Ka), apparent steady state volume of distribution (Vdss/F), and apparent total clearance (CL/F) were computed with the APIS software using blood level profiles from 34 patients divided into four groups: patients receiving either CBZ-CO or CBZ-CR in monotherapy, or CBZ-CO or CBZ-CR in comedication with PB.

Ursodeoxycholate improves hepatobiliary dysfunction induced by valproate-carbamazepine treatment in the rat.

Carbamazepine (CBZ) and valproate (VPA) are commonly used antiepileptic drugs. These drugs, either alone or combined, may produce hepatotoxicity. We report results of a biochemical and histological study of the liver in rats treated for eight days with VPA (500 mg/Kg/day), CBZ (200 mg/Kg/day) and VPA plus CBZ.

Steady state pharmacokinetics of conventional versus controlled-release carbamazepine in patients with epilepsy.

The purpose of the present study was to compare the pharmacokinetic parameters of two carbamazepine (CBZ) tablet formulations (conventional (CBZ-CO) and controlled-release (CBZ-CR)) in patients with epilepsy receiving the drug as monotherapy or polytherapy. The absorption rate constant (Ka), steady-state volume of distribution (Vdss) and total clearance (CL) were computed with the APIS software using 31 blood level profiles from 23 patients who were divided into four groups: patients receiving CBZ-CO in polytherapy, the same patients switched to CBZ-CR in the same polytherapy conditions, patients receiving CBZ-CO in monotherapy and patients receiving CBZ-CR in monotherapy. The four groups were compared in order to assess the significance of differences in Ka, Vdss, CL and diurnal fluctuations of plasma CBZ concentration.

Interactions between clobazam and standard antiepileptic drugs in patients with epilepsy.

We retrospectively collected plasma level assessments performed in 96 adult patients with epilepsy on stable monotherapy, including 9 patients on clobazam (CLB), 34 on carbamazepine (CBZ), 24 on phenobarbital (PB), 9 on phenytoin (PHT), and 20 on valproate (VPA); these results were compared to those obtained in 54 adult patients on stable bitherapy with the association of CLB with either CBZ (n = 17), PB (n = 17), PHT (n = 5), or VPA (n = 15). Our results show that CLB has no significant effect on the level to dose ratio (LDR) of CBZ, PB, PHT, or VPA. Conversely, CBZ, PB, and PHT significantly decrease the LDR of CLB.

Distribution of carbamazepine and its epoxide in blood compartments in adolescent and adult epileptic patients.

Carbamazepine (CBZ) used in the treatment of epilepsy, is metabolized in man to an active metabolite: carbamazepine 10-11 epoxide (CBZ-E). CBZ and CBZ-E concentrations in the different blood compartments (plasma ultrafiltrate, plasma proteins, and red blood cells (RBC)) of epileptic patients on CBZ monotherapy were assessed using HPLC. The highest CBZ and CBZ-E level to dose ratios were observed in the RBC.