Disposition of Propoxyphene and Propranolol in Children

The disposition of propoxyphene and propranolol was studied in children by means of two protocols which minimized the number of blood samples taken from each child. Propoxyphene and its metabolite, norpropoxyphene, were measured in two plasma samples obtained from different children at various times after a single oral dose. These data were pooled and a plasma concentration/time curve was obtained which was consistent with an average T 1/2 of 3.5 hr in this population. The bioavailability of tablets and a solution of propranolol was compared with a crossover design by obtaining plasma samples at the end of the dosage interval during chronic oral administration of various doses. No clear differences in the bioavailability of the two formulations could be detected. Both drugs showed marked interindividual differences in plasma concentrations following oral administration. These findings are consistent with the high hepatic extraction ratio and large presystemic (first pass) effect previously described in adults. The large individual variability supports the concept of monitoring plasma levels as an aid to therapy and demonstrates that the use of a weight-adjusted dose in children can be only an approximation for initial treatment.