Carbamazepine revisited in a monkey model

In a previous study on carbamazepine (Lockard et al., 1974), the problem of its low bioavailability in solid form and its short half-life in monkey were addressed. The present research was designed to evaluate carbamazepine under constant-rate intravenous infusion in our alumina-gel monkey model. Since carbamazepine is insoluble in an aqueous solution, polyethylene glycol 400 was used as the vehicle for administration of this drug to a group of 8 epileptic monkeys. The attenuation of seizures by carbamazepine was not statistically significant since the serum levels of carbamazepine after enzyme induction were less than 2.0 micrograms/ml. This study (a) illustrates that some problems in drug evaluation may be insoluble with our present technology even though we are cognizant of them; (b) makes explicit the fact that the efficacy of carbamazepine is a function of adequate serum levels; (c) demonstrates endogenous oscillations of carbamazepine serum concentrations; and (d) reports simultaneous serum levels of carbamazepine and its 10--11 epoxide in the monkey model.