Kinetics of theophylline in apnea of prematurity in small for gestational age babies.

ABSTRACT

OBJECTIVES: To study the pharmacokinetics of theophylline and its correlations to pharmacodynamic effects in apnea of prematurity in small for gestational age babies. DESIGN: Prospective case control study. SETTING: Level III Neonatal Intensive Care Unit. SUBJECTS: Ten small for gestational age (SGA) babies and 10 gestation matched appropriate for gestational age (AGA) babies with recurrent apnea of prematurity. METHODS: All babies were investigated to exclude secondary causes of apnea. 5 mg/kg of aminophylline loading dose followed by 2 mg/kg as maintenance dose every 8 hourly intravenously was used. The trough and peak levels of theophylline were assessed on different days of therapy. Clinical monitoring was done for the efficacy and toxicity of the drug. Analysis was done using unpaired Student's 't' test and the correlation between plasma theophylline levels of different days was performed by using ANOVA. RESULTS: The therapeutic drug levels were achieved within 24 hours in all babies. The SGA babies showed 25% higher drug levels as compared to AGA babies. The mean trough plasma theophylline levels ranged from 8.15 +/- 1.59 to 12.37 +/- 1.54 micrograms/ml in SGA babies while in AGA babies they ranged from 6.26 +/- 1.93 to 9.96 +/- 1.96 micrograms/ml in first 8 days of therapy. The mean peak levels in SGA babies ranged from 11.91 +/- 1.84 to 17.13 +/- 1.63 micrograms/ml and in AGA babies ranged from 8.17 +/- 1.84 to 13.02 +/- 1.48 micrograms/ml. Twenty per cent SGA and AGA babies each developed clinical toxicity though toxic drug levels were found in 50% SGA and 30% AGA babies. CONCLUSION: There is a need to modify dosage schedule for these babies.