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Neonatal Med > Volume 24(1); 2017 > Article
Neonatal Medicine 2017;24(1):20-25.
DOI: https://doi.org/10.5385/nm.2017.24.1.20    Published online February 28, 2017.
Clinical Pharmacokinetics of Caffeine in Korean Preterm Infants with Apnea of Prematurity.
Myung Seop Lim, Mi Jeong Son, Jung Eun Shin, Soon Min Lee, Ho Sun Eun, Min Soo Park, Kook In Park, Ran Namgung
1Department of Pediatrics, Yonsei University College of Medicine, Seoul, Korea. smlee@yuhs.ac
2Department of Pharmacology, Yonsei University College of Medicine, Seoul, Korea.
Abstract
PURPOSE
Caffeine shows wide interindividual pharmacokinetic (PK) variation, and therapeutic drug monitoring (TDM) may be needed. The PK profile of caffeine in Korean preterm neonates was investigated, and factors influencing the clearance of caffeine were analyzed.
METHODS
Fifty-nine preterm neonates receiving caffeine for apnea of prematurity were enrolled in the study (gestational age, 29.5±2.2 weeks and birth weight [BW], 1,318±358 g). Caffeine (20 mg/kg) was intravenously administered to each neonate as a loading dose, followed by a maintenance dose of 5-10 mg/kg/d. A total of 190 serum concentrations were measured for population PK analysis and modeling using nonlinear mixed-effects model (NONMEM®) software.
RESULTS
The mean serum concentration of caffeine was 15.4±4.5 mg/L (range 7.8-33.0 mg/L). High serum concentrations (>20 mg/L) were noted in 36 samples (29%). At the first measurement of serum caffeine, the mean postmenstrual age was 33.9±2.3 weeks, mean BW was 1,802±471 g, mean duration of treatment was 7.4±9.4 days, and mean sampling time after the last dose was 21.8±2.1 hours. In the population PK analysis, the clearance was 0.033 L/h and volume of distribution was 0.371 L. Typical clearance was calculated as 0.0293×(BW/70)1.33. Among the subjects receiving 5 mg/kg/d caffeine, the most significant risk factor associated with high serum concentrations (>20 mg/L) was low BW (P=0.024).
CONCLUSION
BW was the only covariate that influenced caffeine clearance in preterm neonates. Preterm neonates with low BW should be carefully monitored for apnea and adverse reactions in addition to undergoing TDM.
Key Words: Apnea of prematurity, Caffeine, Clearance, Pharmacokinetics


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