Carbamazepine extended-release capsules vs. oxcarbazepine: computer simulations of the effect of missed doses on drug plasma concentrations

Abstract

The ultimate goal of antiepileptic therapy is a seizure-free state without side effects. The current computer simulation study indicates that AEDs such as CBZ-ERC and OXC, which produce relatively stable plasma concentrations, should be useful in attaining this goal. Nonetheless, simulated plasma concentrations resulting from CBZ-ERC treatment tended to oscillate less dramatically compared with simulated plasma concentrations resulting from treatment with 600 or 1200 mg OXC.

The effect of poor compliance on the pharmacokinetics of carbamazepine and its epoxide metabolite using Monte Carlo simulation

“…The latter can be defined as the concentration (or range of concentrations) that has been empirically found to produce the optimal response in the individual patient (ie, complete seizure control without undesired effects or, if that goal is not achievable, the best compromise between seizure suppression and concentration-related adverse effects). Therefore, in our study, the therapeutic range, instead of the reference range employed in the previous studies [21,22,28,29] , was used to assess the effect of missed or delayed doses and to make dose recommendations.…”

“…Reference: the model was based on a 60-kg compliant epilepsy patient whose K a of CBZ was 1.2 /h and ω Ka was fixed to zero. [21,22] previously investigated the effect of delayed and missed doses on the concentration of the extended release capsule of CBZ. In these two studies, the pharmacokinetic parameters used for simulation were derived from 12 healthy volunteers, and the impact of covariates, such as weight, dose and comedications was not considered.…”

Pharmacokinetic simulations of topiramate plasma concentrations following dosing irregularities with extended-release vs. immediate-release formulations

“…Computer simulation is a cost-effective means of systematically evaluating many different permutations of drug administration and has been used to evaluate the PK impact of irregular dosing for several AEDs in order to determine appropriate corrective actions [15][16][17][18][19]. For ease of illustration, the concentration-time profiles presented in our analysis depict the "typical patient" based on the population mean for each dosing scenario, similar to simulations comparing XR and IR formulations of lamotrigine [19].…”

Historical Review of Carbamazepine for the Treatment of Bipolar Disorder

“…Also, kindling-like processes have been suggested to explain, at least in part, the cyclic nature of both illnesses. 12,13 The effect of antiepileptic drugs on sodium channels, ␥-aminobutyric acid function, and glutamate are the predominant targets of drug action in the psychopharmacologic management of mood disorders.…”

“…25,26 Relative to immediate-release formulations, the use of extended-release formulations resulted in similar parent:epoxide metabolite concentration ratios and AUC values, but a lower degree of plasma concentration fluctuation and intravariability in absorption. 12,21,27,28 Carbamazepine is metabolized primarily to the active 10,11 epoxide metabolite and to a lesser extent by aromatic hydroxylation to 2-and 3hydroxycarbamazepine and 2,3-dihydroxycarbamzepine. Several other metabolites have been identified.…”