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Effect of phenobarbital administration on theophylline clearance in premature neonates
R J Kandrotas1, T L Cranfield, P Gal
1Greensboro Area Health Education Center, North Carolina.
Insights
Phenobarbital does not significantly alter theophylline clearance in premature neonates. While both groups showed increased clearance over time, the addition of phenobarbital did not necessitate dosage adjustments for aminophylline. Monitor theophylline levels closely due to potential rapid changes.
Area of Science:
- Neonatal Pharmacology
- Clinical Pharmacy
- Pediatric Drug Metabolism
Background:
- Theophylline is commonly used for apnea of prematurity.
- Phenobarbital is often administered to neonates for various conditions.
- The interaction between phenobarbital and theophylline clearance in neonates requires investigation.
Purpose of the Study:
- To evaluate the effect of phenobarbital on theophylline clearance in premature neonates.
- To determine if phenobarbital administration necessitates adjustments in aminophylline dosage.
Main Methods:
- A study involving 24 premature neonates receiving aminophylline.
- One group received concomitant phenobarbital therapy, while the control group did not.
- Theophylline clearance was measured weekly over a minimum of 8 weeks.
Main Results:
- Both groups showed an increase in mean theophylline clearance over time.
- The rate of increase in theophylline clearance was not significantly different between groups.
- Theophylline clearance in neonates receiving phenobarbital was comparable to those receiving aminophylline alone.
Conclusions:
- Concomitant phenobarbital administration does not significantly alter theophylline clearance in premature neonates.
- Aminophylline dosage adjustments are not solely indicated based on phenobarbital use.
- Close monitoring of theophylline concentrations is recommended due to potential rapid and unpredictable changes in neonates.
Abstract:
The effect of phenobarbital administration on theophylline clearance was studied in 24 premature neonates. Aminophylline was administered according to a standard protocol of 6 mg/kg loading dose followed by a maintenance dose of 2.5-5 mg/kg/12 h. Of the 24 neonates studied, 12 received a mean phenobarbital dose of 26.34 mg/kg/d (ranging from 2 mg every 24 h to 25 mg every 12 h) and the mean phenobarbital concentration was 56.12 micrograms/ml (range 22-112 micrograms/ml). The remaining 12 patients did not require phenobarbital therapy but did receive aminophylline alone. The two groups were closely matched for gestational age, 5-min Apgar scores, and sex (p greater than 0.2). Steady-state theophylline clearance was determined at least once a week for four or more separate weeks. The study lasted a minimum of 8 wk and if more than one theophylline clearance was determined in any given week, the mean of these clearances was used. Both groups demonstrated an increase in mean theophylline clearance over time (from 15.75 and 16.67 ml/h/kg to 30.33 and 35.42 ml/h/kg for the aminophylline and aminophylline plus phenobarbital groups, respectively). The mean slope, an indicator of the average change in theophylline clearance, was 2.19 for the aminophylline group and 3.27 for the aminophylline plus phenobarbital group (p greater than 0.2), indicating that the theophylline clearance for neonates receiving phenobarbital was not significantly different from that for neonates receiving aminophylline alone. Based on this information, aminophylline does not need to be adjusted solely based on concomitant phenobarbital administration; however, theophylline concentrations should be monitored since theophylline clearance can change rapidly and unpredictably in neonates.