Serum Theophylline Concentrations in very Preterm Neonates Receiving Intravenous Aminophylline for Apnea

Objective: To determine the percentage of neonates who achieved therapeutic theophylline level (TTL) after receiving standard IV loading/maintenance aminophylline doses. To assess factors associated with achieving therapeutic theophylline concentrations and to describe adverse effects of aminophylline.Materials and Methods: This was a pilot, cross-sectional study. Preterm neonates ≤34 weeks’ gestation for which aminophylline was indicated for treatment of apnea were enrolled. Standard IV aminophylline dosage is 8 mg/kg loading dose, followed by 1.5 mg/kg maintenance dose every 8 hours. Serum theophylline concentrations were measured prior to the 8th maintenance dose. Descriptive statistics, univariate and multivariate analyses were performed.Results: Twenty-five neonates (52% female) were enrolled: mean (standard deviation) gestational age and birth weight were 30.4 (2) weeks and 1,277 (415) grams, respectively. Aminophylline was initiated at a median (25%tile, 75%tile) postnatal age of 4 (1, 8) days. Baseline heart rate prior to the loading dose was 153 (13) beats-per-minute. Sixty percent of neonates achieved a therapeutic theophylline level. In the univariate analysis, being male and postnatal age ≤5 days were associated with successfully achieving a TTL. After adjusting for gender, postnatal age ≤5 days was the only factor associated with achieving a TTL (adjusted odds ratio 17.7, 95% confidence interval: 1.9, 164.4). Tachycardia and feeding intolerance were observed in 44% and 24% of neonates, respectively.Conclusion: Current IV aminophylline dosing conditions in Thailand achieved TTL in approximately two-thirds of neonates, suggesting therapeutic drug monitoring is beneficial for guiding dosing. A higher maintenance dose could be considered for neonates older than 5 days.

CYP1A2 Gene Polymorphism and Theophylline Level in Asthma

BACKGROUND: Aminophylline (theophylline) is one of the most frequent asthma therapies in Indonesia, although it remains as a narrow therapy. The effects of drugs are individualized and strongly influenced by genetic, one of which is CYP1A2 gene polymorphisms. This study aimed to determine the profile of CYP1A2 polymorphism and theophylline level in asthma exacerbation patients receiving intravenous aminophylline therapy.METHODS: This cross sectional study was conducted in the emergency room (ER), to adults asthma exacerbation patients without complication (n=27), visiting the ER. The gene polymorphism data were compared with theophylline levels in the blood using chi-square test.RESULTS: In the CYP1A2 gene polymorphism profile, the most common heterozygous alleles are T/G genotype of CYP1A2*1E and C/A genotype of CYP1A2*1F. Most homozygote alleles exist in CYP1A2*1D and CYP1A2*1F. There was significant difference between CYP1A2*1D (p<0.005), CYP1A2*1E (p<0.023) and CYP1A2*1F (p<0.000) polymorphisms and theophylline level.CONCLUSION: CYP1A2*1D, CYP1A2*1E and CYP1A2*1F gene polymorphisms had an effect on theophylline levels. However, no one experienced an overdose theophylline, and no correlation between theophylline levels with CYP1A2 gene polymorphism.KEYWORDS: exacerbation asthma, intravenous aminophylline, CYP1A2 polymorphism gene, theophylline

Treatment of Theophylline Poisoning

To the Editor.— We were interested in the report by Shannon and co-workers1 in which they described the use of multiple exchange transfusions for the treatment of an accidental toxic serum theophylline level in an infant in the postoperative phase of an arterial switch procedure. Although we have no problem with the rationale used for an invasive procedure that has multiple complication risks, we would like to emphasize the option for the use of activated charcoal products in infants who are able to tolerate orally administered medications.