1998 Volume 24 Issue 6 Pages 642-651
The effects of concomitant antiepileptic drugs on the serum valproic acid concentration (Cs) were investigated. Primidone (PRM), phenobarbital (PB), carbamazepine (CBZ), phenytoin (PHT), zonisamide (ZNS), clonazepam (CZP) and ethosuximide (ETS) were coadministrated with valproic acid (VPA).
The routine therapeutic drug monitoring data, obtained from epileptic patients who were treated with the repetitive oral administration of the sustained-release preparations of VPA (VPAR), were used for the analysis. A total of 233 patients were administrated VPA-R alone, and 87, 21 and 6 patients were coadministrated one, two and three different antiepileptic drugs, respectively
Using the data obtained from the patients administrated VPA-R alone, Ct could be expressed conveniently as a function of X as Ct=AXB (X: VPA daily dose per modified body weight. A, B: parameter)
By comparing the regression line on logG vs. logX for VPA-R alone with that for VPA-R plus one concomitant drug, Ct was thus found to be affected at each definite ratio by PB, CBZ, PHT, but not by ZNS.
Next, we defined the parameter Ri (i=1, 2, ..., 7) as a coefficient representing the effect of each concomitant antiepileptic drug on G. All data were analyzed to estimate Ri, using a model based on the assumption that each Ri was independent from one another and multiplicative. The analysis clarified that PB, CBZ and PHT lowered Ct to 0.879, 0.812 and 0.833 times, respectively. On the other hand, ZNS did not affect Ct. The number of patients coadministrated PRM, CZP and/or ETS was not sufficient to detect the effect on Ct based on a test of significance.
