Population pharmacokinetics of theophylline in very premature Japanese infants with apnoea.
OBJECTIVE
To estimate the population pharmacokinetics of theophylline in very premature infants using the non-linear mixed effects modelling.


METHODS
A total of 167 serum concentration measurements obtained from routine theophylline monitoring of 107 very premature Japanese infants were collected.


RESULTS
The final pharmacokinetic parameters were CL (mL/h) = [6.98 . body weight (BW) (kg)(2.17) + 0.244 . post-conceptional age (weeks)] . 1.24(oxygen support), Vd (L) = 0.492 . BW (kg) and F = 0.660, respectively. Clearance was increased by 24% for patients receiving oxygen support. The inter-individual variabilities in clearance and apparent volume of distribution were 15.6% and 80.4%, respectively, and the residual variability was 34.2% as a coefficient of variation.


CONCLUSIONS
Application of the findings in this study to patient care may permit selection of an appropriate initial maintenance dosage to achieve target theophylline concentrations, thus enabling the clinician to achieve the desired therapeutic effect in very premature Japanese infants.
Fukuda
T
T
Department of Pharmacy, Kumamoto City Hospital, Japan.
Yukawa
E
E
Kondo
G
G
Maeda
T
T
Shin-o
T
T
Kondo
Y
Y
Imamura
T
T
Irikura
M
M
Irie
Tetsumi
T
D001049:Apnea / Q000188:drug therapy* / Q000378:metabolism; D044466:Asian People; D001993:Bronchodilator Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D008954:Models, Biological; D015203:Reproducibility of Results; D012189:Retrospective Studies; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
D001993:Bronchodilator Agents; D013806:Theophylline