BRAIN DELIVERY OF CARBAMAZEPINE DURING INTRAVENOUS ADMINISTRATION OF POLYETHYLENE-GLYCOL AND 2-HYDROXYPROPYL-BETA-CYCLODEXTRIN FORMULATIONS

2-hydroxypropyl-beta-cyclodextrin has recently been used to solubilize carbamazepine for the development of a parenteral formulation. Microd ialysis studies in rabbits were conducted to determine if 2-hydroxypro pyl-beta-cyclodextrin affects the distribution of carbamazepine and it s active metabolite, carbamazepine-10,11-epoxide, into the brain. No s tatistically significant differences in the brain distribution or syst emic elimination of carbamazepine and carbamazepine-10,11-epoxide were observed. In addition, there was no differential distribution of drug or metabolite into cortex and ventricle. The differences in brain to plasma area under the concentration-time curve ratios between parent d rug and metabolite appear to reflect the difference in plasma free fra ction of the two compounds. It is concluded that 2-hydroxypropyl-beta- cyclodextrin does not affect brain distribution of carbamazepine and c arbamazepine-10,11-epoxide, while no hemolytic effects were observed i n the use of this complexing agent. These findings support the use of 2-hydroxypropyl-beta-cyclodextrin in the development of a parenteral f ormulation of carbamazepine.