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. The results show that the lowest dispersion of pharmacokinetic parameters was in patients receiving CBZ-CR in monotherapy. The CBZ formulation alters CBZ Ka, (Vdss/F) and (CL/F) values. CBZ (CL/F) also depends on the treatment (presence or absence of comedication by PB). In patients receiving PB in comedication with CBZ, the formulation of CBZ has no effect on PB pharmacokinetic parameters. These changes may be clinically significant and should be taken into account.