[Population pharmacokinetic analysis of two theophylline formulations in premature neonates and infants with apnea].
A study was conducted to clarify differences in the theophylline pharmacokinetics of two orally available products, theophylline alcohol and Apnecut, in premature neonates and infants using population pharmacokinetic analysis. Fifty-two patients with apnea hospitalized at the National Center for Child Health and Development were enrolled (total number of plasma concentration points=90). Population pharmacokinetic analysis under steady-state conditions was performed using NONMEM ver. V. The mean oral clearance was 0.0249 (l/h), and the inter- and intraindividual variation was 30.3% and 28.3%, respectively, in the basic model. The oral clearance was significantly affected by body weight, sex, and age. The final model obtained was expressed by the following equation: oral clearance (l/h)=0.0201 x (body weight (g)/1000)(1.08)x (1-0.282 x drug product), where theophylline alcohol is 0 and Apnecut is 1. The inter- and intraindividual variations in the final model were 15.0% and 15.3%, respectively. The oral clearance of the two oral formulations differed significantly, and this difference should be considered when adjusting the theophylline dose.
Suda
Yasuyo
Y
Course of Clinical Pharmacy, Graduate School of Pharmaceutical Science, Meiji Pharmaceutical University, Kiyose City, Tokyo, Japan.
Hanada
Kazuhiko
K
Tsuchiwata
Shin-Ichi
S
Saito
Makoto
M
Nakamura
Tomoo
T
Ito
Yuji
Y
Ishikawa
Yoichi
Y
Kushida
Kenji
K
Ogata
Hiroyasu
H
D000284:Administration, Oral; D001049:Apnea / Q000188:drug therapy*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature; D008297:Male; D008954:Models, Biological; D013806:Theophylline / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D001993:Bronchodilator Agents; D013806:Theophylline