Does percent reduction in seizure frequency correlate with plasma concentration of anticonvulsant drugs? Experience with four anticonvulsant drugs.

Autor: Mahmood I; Office of Clinical Pharmacology and Biopharmaceutics, Division of Pharmaceutical Evaluation I (HFD-860), Food and Drug Administration, Rockville, MD 20852, USA., Tammara VK, Baweja RK
Jazyk: angličtina
Zdroj: Clinical pharmacology and therapeutics [Clin Pharmacol Ther] 1998 Nov; Vol. 64 (5), pp. 547-52.
DOI: 10.1016/S0009-9236(98)90138-2
Abstrakt: Objective: To investigate the relationship between the percentage reduction in seizure frequency in patients with epilepsy and plasma concentrations after oral administration of 4 anticonvulsant drugs.
Methods: Patients with a minimum of 25% reduction in their seizure frequency from their baseline value were declared responders. The percentage reduction in seizure frequency was plotted against plasma concentrations with use of pharmacodynamic models (linear, log-linear, Emax, and sigmoidal Emax models). In addition to pharmacodynamic models, a logistic regression model was also fitted to the concentration-response data, with a value of 1 for responders and 0 for nonresponders.
Results: The concentration-effect relationship could not be adequately described either by the pharmacodynamic models or by the logistic regression analysis.
Conclusions: Based on the results obtained from both pharmacodynamic models and logistic regression analysis the percentage reduction in seizure frequency may not be a true surrogate marker for anticonvulsant drugs to establish a pharmacodynamic relationship with plasma concentrations.
Databáze: MEDLINE
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