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Clinical Pharmacokinetics of Caffeine in Korean Preterm Infants with Apnea of Prematurity

Authors
 Myung Seop Lim  ;  Mi Jeong Son  ;  Jung Eun Shin  ;  Soon Min Lee  ;  Ho Sun Eun  ;  Min Soo Park  ;  Kook In Park  ;  Ran Namgung 
Citation
 Neonatal Medicine, Vol.24(1) : 20-25, 2017 
Journal Title
 Neonatal Medicine 
ISSN
 2287-9412 
Issue Date
2017
Keywords
Apnea of prematurity ; Caffeine ; Clearance ; Pharmacokinetics
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.
Files in This Item:
T201701565.pdf Download
DOI
10.5385/nm.2017.24.1.20
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아청소년과학교실) > 1. Journal Papers
Yonsei Authors
Namgung, Ran(남궁란) ORCID logo https://orcid.org/0000-0001-7182-9535
Park, Kook In(박국인) ORCID logo https://orcid.org/0000-0001-8499-9293
Park, Min Soo(박민수) ORCID logo https://orcid.org/0000-0002-4395-9938
Shin, Jeong Eun(신정은) ORCID logo https://orcid.org/0000-0002-4376-8541
Eun, Ho Seon(은호선) ORCID logo https://orcid.org/0000-0001-7212-0341
Lee, Soon Min(이순민) ORCID logo https://orcid.org/0000-0003-0174-1065
Lim, Myung Seop(임명섭)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154449
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