Measurement of phenytoin and carbamazepine in an ultrafiltrate of saliva

We have introduced a method of collecting a prepurified sample of saliva in the mouth for the quantitative determination of phenytoin and carbamazepine. The patient places in the mouth an osmotic device that accumulates in greater than 8 min a volume of approximately 1.2 ml clear ultrafiltrate devoid of molecules greater than 12,000 daltons. The concentrations of phenytoin and carbamazepine in serum (total and free fractions), whole saliva, and the salivary ultrafiltrate from patients receiving anticonvulsant treatment were measured and correlated. The correlation coefficients r (p less than 0.001) for phenytoin were: total in serum and ultrafiltrate r = 0.92; free in serum and ultrafiltrate r = 0.93; whole saliva and ultrafiltrate r = 0.95. The correlation coefficients for carbamazepine were (in the same order) 0.90, 0.92, and 0.93. It is concluded that the use of an ultrafiltrate as a biological medium simplifies the diagnostic evaluation of free circulating phenytoin and carbamazepine concentrations for monitoring therapy.