Tears as the Best Practical Indicator of the Unbound Fraction of an Anticonvulsant Drug

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Abstract
Phenobarbital and carbamazepine concentrations were determined by the EMIT [enzyme multiplied immunoassay] technique in tears, saliva, CSF and plasma of patients with epilepsy. Closer correlation was shown between tear/plasma and tear/CSF ratios than between saliva/plasma and saliva/CSF ratios for the 2 agents. The phenobarbital CSF/serum ratio was in good agreement with data in the literature, and the higher ratio found for carbamazepine may be caused by an EMIT assay cross-reaction for the free fraction of carbamazepine-10,11-epoxide. Tears seem to represent the best practical indicator of the unbound fraction of an anticonvulsant drug, and the noninvasiveness of the method makes it specifically useful in pediatric neurology.