By intrapatient comparison atconstant phenytoin (PUT) dose, the effect of increased carbamazepine (CBZ) dose was studied in 32 epileptic outpatients treated with a combination of PHT and CBZ. The mean PHT plasma concentration, as well as the concentration/dose ratio for PHT, became significantly higher secondary to increased doses of CBZ (14.1 plusmn; 3.5 vs. 19.3 plusmn; 3.6 mu;g/ml and 2.8 plusmn; 1.0 vs. 3.9 plusmn; 1.4 mu;g/ml plasma per milligram/kilogram daily dose, respectively; p 0.001). Concomitantly, in spite of CBZ dose higher by 17.6percnt;, the CBZ concentration increased by only 6.4percnt;, and the CBZ concentration/dose ratio actually decreased by 10percnt;. In contrast, by intrapatient comparison atconstant CBZ dose, the effect of reduced PHT dose on CBZ was studied in 22 patients. The mean CBZ plasma concentration as well as the concentration/dose ratio for CBZ appeared significantly higher, with a concomitant reduction of PHT (6.7 plusmn; 1.6 vs. 8.6 plusmn; 1.6 mu;g/ml and 0.37 plusmn; 0.1 vs. 0.49 plusmn; 0.2 mu;g/ml plasma per milligram/kilogram daily dose, respectively; p 0.001). This simultaneous dual effectmdash;inhibition of PHT metabolism by CBZ and induction of CBZ metabolism by PHTmdash;can result in PHT intoxication along with a fall in CBZ plasma concentration to a subtherapeutic range. This effect may be avoided or reduced if the PHT concentration is adjusted to sim;13 mu;g/ml before CBZ is added or increased.
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