Theophylline Therapy in Idiopathic Apnea of Prematurity — Optimum Plasma Concentration and Pharmacokinetics —

Abstract

The efficacy of oral theophylline as a 10 % alcoholic solution at a dose of 2 mg/kg/12 hr was examined in 15 premature infants with idiopathic apnea. With a plasma theophylline concentration of 6.3±0.8μg/ml (mean ± S.E.) or total methylxanthine as a theophylline (theophylline + caffeine) concentration of 7.8±1.2 μg/ml, all infants experienced complete cessation of apneic spells. Mild adverse effects such as tachycardia and vomitting were observed in 2 infants with plasma theophylline concentration of 8 to 9 μg/ml. Since both the effective and the toxic concentration of theophylline varied from infant to infant, the optimum concentration of theophylline should be adjusted individually. In a pharmacokinetic study, the plasma half-life of theophylline in 5 infants was 23.5±2.3 hr and the apparent volume of distribution in 4 infants was 0.81±0.04 1/kg. The plasma elimination rate constants of theophylline increased with postnatal age or postconception age (gestational age + postnatal age) and correlated significantly with postconception age. A dosage adjustment is needed in long-term therapy of apnea in premature infants according to their postconception age. © 1985, The Japanese Society of Clinical Pharmacology and Therapeutics. All rights reserved.