CSF/SERUM THEOPHYLLINE RATIOS IN YOUNG PREMATURE INFANTS

Abstract

Theophylline is widely used in neonatal intensive care units for respirogenesis & bronchodilation. It is important to understand the pharmacokinetics of this drug in premature infants. There are reports of fixed correlation between CSF & blood theophylline levels in premature infants beyond the neonatal period, older children & adolescents. During evaluations for sepsis simultaneous blood & CSF specimens were obtained in 12 premature infants (B.W. 785 gm - 1505 gm), including 9 neonates, who were receiving I.V. theophylline and were in steady state. One subject was studied twice. Theophylline assay was by HPLC. In contrast to earlier reports, subjects revealed no constant or predictable relationship between serum & CSF theophylline levels. CSF/serum ratios varied from 41% - 106% with a mean of 78%. The subject studied twice demonstrated ratios of 57% and 82%. Variables considered to account for these divergent observations included age, intracerebral hemorrhage, culture proven sepsis and/or meningitis, serum albumin/total proteins, & other concurrent medications. No variable or combination of variables could explain the great scatter observed. It was concluded that young premature infants exhibit unpredictable and highly variable correlation between CSF & serum theophylline levels. Considerable intersubject variability may occur without obvious cause. This agent should be used in this patient group with realization that the CSF level may be 100% of the serum level or less than 50% thereof.