Population pharmacokinetic analysis of two theophylline formulations in premature neonates and infants with apnea

Suda, Y.; Hanada, K.; Tsuchiwata, S-Ichi.; Saito, M.; Nakamura, T.; Ito, Y.; Ishikawa, Y.; Kushida, K.; Ogata, H.

Yakugaku Zasshi Journal of the Pharmaceutical Society of Japan 128(4): 635-640

2008


ISSN/ISBN: 0031-6903
PMID: 18379181
DOI: 10.1248/yakushi.128.635
Accession: 032869229

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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 (1/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 (1/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.