Back to Search
Start Over
Developmental population pharmacokinetics of caffeine in Chinese premature infants with apnoea of prematurity: A post-marketing study to support paediatric labelling in China
- Source :
- British journal of clinical pharmacologyREFERENCES. 87(3)
- Publication Year :
- 2020
-
Abstract
- Aims The aim of the study was to evaluate the suitability of the current caffeine dosing regimen for the Chinese population using modelling and simulation approach. Methods Pharmacokinetic samples were collected from 99 Chinese newborns with premature apnoea. The median (range) of gestational age and postmenstrual age were 28.3 (25.0-33.4) weeks and 31.1 (26.4-38.0) weeks, respectively. Newborns were receiving caffeine citrate at a loading dose of 20 mg/kg/d and a maintenance dose of 5-10 mg/kg/d. Caffeine concentrations and CYP1A2 polymorphisms were investigated. Population pharmacokinetic modelling of caffeine in Chinese preterm newborn on a population-wide scale was conducted using NONMEM. Results A 1-compartment model with first-order elimination was used to describe population pharmacokinetic. With current weight implemented using 0.75 allometric scaling, clearance (CL) was positively related to current weight and postmenstrual age, but a negative relationship was observed with serum creatinine concentration. Eight genotypes of CYP1A2 were tested and none of them had a significant impact on caffeine pharmacokinetic parameters. Interindividual variability of CL and volume of distribution was 7.70 and 65.9%. The median (range) of 95% confidence intervals of CL were 0.0128 (0.0128-0.0131) L/h/kg. Monte Carlo simulation demonstrated that 80% (loading dose) and 98% (maintenance dose) of premature infants treated with a labelled dosing regimen attained the concentration target range of 5-20 mg/L. Conclusion A population PK model of caffeine was developed in Chinese newborns. Body weight-implemented allometric scaling, postmenstrual age and serum creatinine concentration markedly affected caffeine clearance. The labelled dosing regimen is suitable for Chinese premature infants.
- Subjects :
- China
Apnea
Population
Physiology
030226 pharmacology & pharmacy
Loading dose
03 medical and health sciences
0302 clinical medicine
Caffeine
Medicine
Humans
Pharmacology (medical)
030212 general & internal medicine
education
Child
Pharmacology
Volume of distribution
Marketing
education.field_of_study
Maintenance dose
business.industry
Postmenstrual Age
Infant, Newborn
Gestational age
Infant
NONMEM
Caffeine citrate
business
Infant, Premature
medicine.drug
Subjects
Details
- ISSN :
- 13652125
- Volume :
- 87
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- British journal of clinical pharmacologyREFERENCES
- Accession number :
- edsair.doi.dedup.....41af06d1be2a7e2ecf93cbe8115fe327