Use of saliva in therapeutic drug monitoring of caffeine in preterm infants

Caffeine is frequently used to treat apnea of prematurity in preterm infant s. Because caffeine has a narrow therapeutic window, plasma concentrations are generally monitored weekly. It would be advantageous to monitor this th erapy without blood sampling; saliva might offer this possibility. Paired p lasma-saliva and saliva-saliva observations were made in preterm infants (n = 140, gestational ages between 24 and 34 weeks) who received caffeine for the treatment of apnea of prematurity. Three methods were used to collect saliva: no stimulation, dilute citric acid on collection gauze, and dilute citric acid in the cheek pouch before collection. Plasma and saliva caffein e concentrations were determined using high-performance liquid chromatograp hy (HPLC). For all collection methods, the plots of the plasma/saliva outco mes showed linear relationships. The correlation between caffeine concentra tion in plasma and saliva and the reproducibility of saliva sampling was be tter with stimulation of saliva production using citric acid in the cheek p ouch (r = 0.89) than with no stimulation (r = 0.68) or with stimulation usi ng citric acid on the collection swab (r = 0.79). Monitoring of caffeine th erapy in saliva can be applied reliably for routine use in clinical practic e, but its reliability and reproducibility depend on the saliva sampling me thod used; saliva stimulation with citric acid in the cheek pouch is the be st method studied.