Compliant populations: variability in serum concentrations.

Safety and efficacy studies of new antiepileptic drugs require strict adherence to prescribed dosage regimens. Therefore, they provide a unique opportunity to investigate the variability in serum concentrations that are seen in a compliant group of motivated patients. Phenytoin and carbamazepine serum concentrations from two safety and efficacy trials were evaluated for coefficient of variation, difference from baseline concentration, and percent difference. Coefficient of variation for phenytoin was usually less than 20% and was not influenced by baseline serum concentration or frequency of administration. There was no relationship between serum concentration and frequency of administration on carbamazepine coefficient of variation which was less than 25% in most cases. Most PHT differences from baseline were within 5 micrograms/ml, whereas most CBZ differences were within 2 micrograms/ml. Most PHT concentrations were within 30% of each other whereas most CBZ concentrations were within 40% of each other. Data from this study provide information regarding the variability of phenytoin and carbamazepine concentrations under ideal conditions and can be used to set limits for fluctuations of concomitant antiepileptic drugs in safety and efficacy trials or ideal patient care settings.