A highly-sensitive microcolumn HPLC method for the simultaneous determination of carbamazepine and carbamazepine-l0,ll-epoxide in human serum and saliva is described. The method was successfully employed for the study of pharmacokinetics of carbamazepine in humans. After oral administration of 100 and 200 mg of carbamazepine to a volunteer, multiple peaks were observed on the kinetic curves. They were symbathic in the serum and saliva. This indicated the presence of multiple peaks which characterize both free and protein-bound fractions of the drug.
The existence of multiple peaks on the kinetic curves implies that the kinetic of carbamazepine cannot be described with the one-compartment linear model. Nevertheless, each peak was treated within the range of a onecompartment linear model of absorption and the results obtained were compared with published data.
For the elucidation of the nature of multiple peaks the graphical differentiation of ascending and descending branches of all peaks were carried out. On this basis the dependence of the absorption and elimination rates on time was constrained. The analysis of experimental data resulted in the following conclusions: (a) the presence of multiple peaks on the kinetic curves is induced by the interrupted character of carbamazepine absorption that is caused by the very poor solubility of carbamazepine; (b) the elimination of the drug from blood serum occurs in two phases. Binding of carbamazepine with tissues takes place in the first phase, and biotransformation and excretion occurs in the second phase. It is possible that the presence of multiple peaks on the kinetic curves is partially caused also by redistribution of the drug from the comparatively easily accessible to the less accessible tissues. This requires further investigation.