Effect of Progabide on Serum Phenytoin and Carbamazepine Concentrations
| Autor: | James C. Cloyd, Graves Nm, Welty Te, Richard C. Brundage, Ilo E. Leppik |
|---|---|
| Rok vydání: | 1987 |
| Předmět: |
Adult
Male Phenytoin medicine.medical_treatment Convulsants Pharmacology Placebo Random Allocation Double-Blind Method Seizures Humans Medicine Pharmacology (medical) gamma-Aminobutyric Acid business.industry Carbamazepine Drug interaction Crossover study Anticonvulsant Toxicity Drug Evaluation Female Neurology (clinical) business medicine.drug Progabide |
| Zdroj: | Clinical Neuropharmacology. 10:545-554 |
| ISSN: | 0362-5664 |
| DOI: | 10.1097/00002826-198712000-00006 |
| Popis: | Progabide (PGB) is a gamma-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 less than 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 greater than 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 less than 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. |
| Databáze: | OpenAIRE |
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