Cross Validation of Serum to Saliva Relationships of Caffeine, Theophylline and Total Methylxanthines in Neonates

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Abstract
We have previously described the relationships of serum and saliva concentrations of caffeine, theophylline and total methylxanthines in premature infants. We have now extended the previous studies in order to validate the previously derived relationships with new data. The new serum to saliva relationships, derived using regression and ratio models, are cross validated against the relationships from the previous data, and vice versa. A good cross validation was observed for caffeine and total methylxanthine concentrations in infants treated with caffeine. In the theophylline treatment group, theophylline concentrations did not cross validate well, whereas the total methylxanthine concentrations did. Since in vivo conversion of theophylline to caffeine and vice versa may affect the individual methylxanthine relationships, the total methylxanthine equatio