Intraindividual Variability of Carbamazepine, Phenobarbital, and Phenytoin Concentrations in Saliva

Abstract

The intraindividual variability of salivary carbamazepine (CBZ), phenobarbital (PB), and phenytoin (PHT) concentrations was studied in six healthy male volunteers. During three consecutive 1-week phases, subjects took one of the antiepileptic drugs (AED) for 5 days. Nine saliva and nine blood samples were collected simultaneously over the last 4 days of each phase. Salivary, unbound serum, and total serum CBZ, PB, and PHT concentrations were determined by fluorescence polarization immunoassay. Individual mean saliva (Cs)/total serum (Ct), unbound serum (Cu)/Ct, and Cs/Cu concentration ratios for CBZ, PB, and PHT were similar to those reported previously. The intraindividual mean (+/- SD) coefficients of variation (%) of the Cs/Ct, Cu/Ct, and Cs/Cu ratios for CBZ were 4.8 +/- 2.2%, 4.4 +/- 1.8%, and 5.0 +/- 1.9%, respectively; for PB they were 5.1 +/- 0.8%, 3.6 +/- 0.9%, and 6.4 +/- 1.0%, respectively; and for PHT they were 7.4 +/- 3.1%, 5.5 +/- 1.2%, and 8.3 +/- 3.2%, respectively. The mean Cs/Ct and Cu/Ct ratios for CBZ and PHT were not significantly different, but they were different for PB (p = 0.01). However, the range of individual coefficients of variation of the Cs/Ct ratio for PB was 4.0-6.2%, which is acceptable for clinical monitoring. We conclude that the intraindividual variability of CBZ, PB, and PHT concentrations in saliva, based upon the saliva/serum concentration ratios of each AED, is not a factor that should dissuade clinicians from using saliva for the therapeutic monitoring of these agents.