title: [Population pharmacokinetic analysis of two theophylline formulations in premature neonates and infants with apnea].
abstract: 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.
authors: Course of Clinical Pharmacy, Graduate School of Pharmaceutical Science, Meiji Pharmaceutical University, Kiyose City, Tokyo, Japan.
authors: Yasuyo
authors: Y
authors: Suda
authors: Kazuhiko
authors: K
authors: Hanada
authors: Shin-Ichi
authors: S
authors: Tsuchiwata
authors: Makoto
authors: M
authors: Saito
authors: Tomoo
authors: T
authors: Nakamura
authors: Yuji
authors: Y
authors: Ito
authors: Yoichi
authors: Y
authors: Ishikawa
authors: Kenji
authors: K
authors: Kushida
authors: Hiroyasu
authors: H
authors: Ogata
mesh_terms: 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*
chemical_list: D001993:Bronchodilator Agents; D013806:Theophylline