Relative bioavailability of two different phenytoin preparations. Evidence for an age dependency

Relative bioavailability (RB) of two commercially available phenytoin preparations showed greater differences in absorption in children than in adults. 93 patients received one or more doses of one or two preparations. Serum assays were made at steady state. Age-matched groups were compared. In another cross-over study, 12 patients received two or more doses of each formulation until steady state levels were reached. 5 adult volunteers received single doses of each preparation, and multiple serum samples were assayed to define the peak blood concentration and area under the curve. To calculate RB, the value of V max/F was determined from plots of serum concentration (C) vs. C/dose (C/D). Bioavailability was greater in the preparation with the smaller crystal size and more rapid in vitro dissolution. Relative bioavailability increased with increasing age, suggesting an age-dependent effect on drug absorption.