Aging variabilities of level-dose relationship in antiepileptic monopharmacy--with reference to drug interaction...

The influences of age, dose and comedication on the dose-level relationship were investigated using the ratio of plasma level to dose per body weight (microgram/ml/mg/kg/day) as an index in patients who had received the therapeutic doses of antiepileptic drug(s) for a long term. Samples of the blood concentrations were taken from 1,922 patients ranging in age from one to 40: 1,567 measured values were obtained under medication with phenobarbital (PB), phenytoin (PHT), carbamazepine (CBZ) or valproate (VPA) alone, and 2,201 under medication with any two of the above-mentioned antiepileptic drugs. With regard to PB, PHT, CBZ and VPA, when used alone, the L/D ratio was the lowest in the youngest age group, increased toward the latter half of teens, reached a peak at about age 20 and slightly decreased in the rest between the 20s and 30s. The age when the L/D ratio changes with aging is consistent with the age when the body weight of children obviously increases. As a result, during such a term, the fairly constant blood concentration can be maintained without overtly changing the daily dose. In the same age group given a single antiepileptic drug, the L/D ratio for PHT steeply increased at the dose of 4 in adults or 5 mg/kg/day in children, while the ratio rather decreased for CBZ and VPA. Clinical considerations should be paid to the fact that there was a non-linear relationship between the dose and the plasma concentration not only of PHT but of CBZ and VPA, and that the turning points were all within the range of therapeutic doses.(ABSTRACT TRUNCATED AT 250 WORDS)