Does percent reduction in seizure frequency correlate with plasma concentration of anticonvulsant drugs? Experience with four anticonvulsant drugs.
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.
Mahmood
I
I
Office of Clinical Pharmacology and Biopharmaceutics, Division of Pharmaceutical Evaluation I (HFD-860), Food and Drug Administration, Rockville, MD 20852, USA.
Tammara
V K
VK
Baweja
R K
RK
D000927:Anticonvulsants / Q000008:administration & dosage / Q000097:blood* / Q000494:pharmacology*; D004311:Double-Blind Method; D004827:Epilepsy / Q000188:drug therapy*; D005444:Flunarizine / Q000097:blood; D005632:Fructose / Q000031:analogs & derivatives / Q000097:blood; D006801:Humans; D000077213:Lamotrigine; D016014:Linear Models; D016015:Logistic Models; D009557:Nipecotic Acids / Q000097:blood; D000078308:Tiagabine; D000077236:Topiramate; D014227:Triazines / Q000097:blood
D000927:Anticonvulsants; D009557:Nipecotic Acids; D014227:Triazines; D000077236:Topiramate; D005632:Fructose; D005444:Flunarizine; D000077213:Lamotrigine; D000078308:Tiagabine