Progabide (PGB) is a γ-aminobutyric acid (GABA)-agonist drug undergoing clinical evaluation for the treatment of spasticity, movement disorders, and epilepsy. Drug interactions were studied during a randomized, double-blind, crossover trial of the efficacy and toxicity of PGB in patients with partial seizures taking phenytoin (PHT) and carbamazepine (CBZ).
In twenty-two of 32 patients (69%) receiving PGB, PHT dosage was reduced, while only four patients (12%) had their dosage reduced during placebo treatment (p < 0.001). Carbamazepine dosage was decreased in five of 32 patients (16%) during the active treatment, while two patients (6%) had a dosage reduction when receiving placebo (p > 0.75). The mean PHT concentrations at the end of baseline, PGB, and placebo treatments were significantly different: 17.5, 20.4, and 16.8 mg/L, respectively (p < 0.05). Nevertheless, careful adjustment of PHT dosage maintained serum concentration within ±25% of target values in both the PGB and placebo periods. Among patients who first received PGB and then placebo, PHT concentrations remained elevated relative to dose suggesting that PGB exerts a prolonged effect on PHT disposition. The addition of PGB to regimens including PHT results in a significant increase in serum PHT concentrations. This drug interaction most likely occurs as a result of PGB mediated inhibition of hepatic microsomal enzymes.
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