Tc. Lee et al., SALIVA AS A VALID ALTERNATIVE TO SERUM IN MONITORING INTRAVENOUS CAFFEINE TREATMENT FOR APNEA OF PREMATURITY, Therapeutic drug monitoring, 18(3), 1996, pp. 288-293
Caffeine is a potentially useful alternative to theophylline for the t
reatment and prevention of apnea of prematurity because of its lower t
oxicity and longer terminal half-life. Monitoring of salivary caffeine
concentrations is less invasive than blood sampling, especially in ve
ry sick premature neonates. Caffeine citrate-3 mg/kg, 15 mg/kg, or 30
mg/kg-was administered once daily for 7 days in a randomized, parallel
design to 59 newborn, premature infants with an initial loading dose
of twice the maintenance dose. Serum and saliva samples (131 pairs) we
re collected and assayed by high-performance liquid chromatography (HP
LC) for caffeine content. Measurable caffeine concentrations in serum
ranged from 0.28 to 93.3 mg/L and in saliva from 0.35 to 91.5 mg/L. Th
e mean ratio of the saliva-to-serum concentrations was 0.924. There wa
s no significant difference in Precision between the serum and salivar
y data, The mean serum caffeine concentration was 29.9 mg/L, and the m
ean salivary concentration was 27.7 mg/L, indicating a small negative
bias for saliva versus serum monitoring. Salivary caffeine concentrati
on monitoring is a satisfactory alternative to blood sampling across a
wide range of caffeine doses used to treat apnea.