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NEUROLOGY 1994;44:1469
© 1994 American Academy of Neurology

Measurement of carbamazepine and carbamazepine epoxide in the human brain using in vivo microdialysis

R. D. Scheyer, MD, M. J. During, MD, D. D. Spencer, MD, J. A. Cramer, BS and R. H. Mattson, MD

Departments of Neurology (Drs. Scheyer and Mattson, and J.A. Cramer) and Surgery (Drs. During and Spencer), Yale University School of Medicine, New Haven; and West Haven VA Medical Center (Drs. Scheyer and Mattson, and J.A. Cramer), West Haven, CT.

We report the first study of carbamazepine and carbamazepine-10,11-epoxide concentrations determined by using intracerebral microdialysis in three patients undergoing depth electrode studies for the evaluation of medically intractable epilepsy. Very small microdialysis catheters, affixed to and inserted with the depth electrodes, sampled drug concentration in the extracellular environment. We perfused artificial extracellular fluid continuously, and varied the perfusion rate to permit estimation of the absolute drug concentration in the extracellular space. Serum samples were obtained simultaneously. The relation between dialysate and extracellular concentration (recovery fraction) depended, in vivo but not in vitro, on the relative lipophilicity of the compounds, suggesting that diffusion of the drug within the brain is a major determinant of microdialysate drug concentration. When this is taken into account, the steady-state extracellular concentrations of these compounds closely mirror their unbound serum concentrations.

Address correspondence and reprint requests to Dr. Richard D. Scheyer, Neurology Service/127, West Haven VA Medical Center, 950 Campbell Avenue, West Haven, CT 06516.

Received November 10, 1993. Accepted in final form February 14, 1994.




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