The relative bioavailability and palsma level flucturation of controlled release carbamazepine (Carbamazepine CR CBZ CR, Tegretol CR) to the regular prokuct (Carbamazepine RR, CBZ RR, Tegretol RR) were studied in 12 patients who were taking
stable
dose
of carbamazepine for more than six weeks. Fixed dosage regilnen (400mg every 12 hours) of both products was administered in a random cross-over manner at least for four days. After reaching steady-state, serial blood samples were drawn after last
dose
administration. Plasma carbamazepine levels were analysed by fluorescence polarizing immunoassay.
The controlled release products showed lower area under the concentration time curve (AUC; 89.7±20.0μg/ml/hr) than that (107.1±13.2μg/ml/hr) of the regular products (p<0.01), and also showed low peak plasma level (CR; 8.48±1.93μg/ml, RR;
10.57±1.55μg/ml). However, fluctuation of plasma drug level during dose interval was slightly less in controlled release products compared with carbamazepine regular products in the respect of various indices such as percent fluctuation,
fluctuation
index and area deviation from mean level However those parameters did not show no statistical singificance between two products except area diviation (p<0.01). Though the controlled relase product showed slightly less fluctuation during dose
interval,
this seemed to be the expense of incomplete bioavalilability.
As a conclusion, the dose correction should be made according to the relative bioavailability of controlled release formulation if switching of the formulation from regular to controlled regular to controlled release formulation if switching of
the
formulation from regular to controlled release form would be needed. However it could not be proved that controlled rolease fromulation had less fluctiuation during dose interval in this study. More detailed studies should be pursued toshow the
evidence
of significant superiority of currently marketing controlled release formulation to the regular one.
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