Use of salivary concentrations in the prediction of serum caffeine and theophylline concentrations in premature infants

Simultaneous blood and saliva samples were drawn for determination of caffeine and theophylline concentrations in 17 infants receiving caffeine or theophylline therapy for apnea of prematurity. The relationship between serum and saliva concentrations in each drug treatment group was explored using (1) regression analysis and (2) serum: saliva ratio. Significant correlations were observed between serum and salivary concentrations. Salivary concentrations approximated 76 to 80% of the serum concentrations based on the derived serum: saliva ratios. When salivary concentrations were less than 8 μg/ml, the serum concentrations did not exceed therapeutic range and no clinical toxicity was noted. Monitoring of salivary drug concentrations as an alternative to serum drug concentrations may be useful in preterm infants on methylxanthine therapy. When salivary concentrations exceed 8 μg/ml, serum concentrations should be determined.