Clinical Pharmacology of Theophylline in Preterm Infants: Effects, Metabolism and Pharmacokinetics
Gian Maria Pacifici.
Recurrent apnea is common in preterm infants with consequent episodes of loss of effective
breathing and the bronchodilator theophylline prevents apnea and reduces the number of apneic attacks.
This drug also reduces hypoxaemic episodes. Theophylline acts on the lungs, kidneys and brain. Theophylline
inhibits solute reabsorption in various segments of the nephron and a marked diuresis which occurs
immediately after the administration of theophylline. This drug ameliorates kidney dysfunction and
prophylaxis given early after birth, preventing vasomotor nephropathy. Theophylline reduces brain activity
and reduces the spontaneous activity transients and alters the sleep-wake state in pre-term infants.
Theophylline is extensively metabolized in premature infants and its major metabolic product is caffeine. The demethylation
pathway occurring predominantly in adults is substituted by N-methylation to caffeine in premature infants. The halflife
of theophylline is 5-fold longer in neonates than in adults and reaches the adult value at the age of 55 weeks. Theophylline
may be administered trans-cutaneously by applying this drug to the back or abdomen of the infants and the mean
fractional absorbance at 30 hours is 0.25. Theophylline is present in saliva and the concentration of this drug in saliva is
similar to that in plasma, saliva may be used to monitor theophylline concentration. In conclusion, theophylline is a useful
drug to treat apnea and ameliorate kidney dysfunction.
Keywords: Effects, development, metabolism, neonate, pharmacokinetics, theophylline.
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