Estimation of Plasma Unbound Phenobarbital Concentration by Using Mixed Saliva

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Abstract
Relationships among plasma total (Ct), plasma protein unbound (Cf) and mixed salivary (Cs) concentrations of phenobarbital (PB) were studied in 29 epileptic patients. A highly significant correlation was observed between Ct and Cf. Although a significant correlation was observed between Cf and Cs, Cs/Cf ratio was only 0.63. When Cs was corrected by using pKa (7.41) and pH of saliva to estimate free PB concentration (Cest f), a highly significant correlation was obtained between Cf and Cest f, and Cest f/Cf ratio was 0.96. The temporal course of Cest f obtained from Cs after an oral single dose of 50 mg PB in a healthy adult male volunteer was approximated as a triexponential equation. The peak time was 2 h after ingestion and apparent half-life was 66 h. The prediction of minimum concentrations at steady state on the basis of these parameters corresponded well with actually obtained Cest f following repetitive PB administration.