Neonates caffeine elimination

Theophylline is an example of a drug that is readily metabolized in neonates by N-methylation to caffeine (process not relevant clinically in older infants, children, and adults). It is also a compound that has pharmacologic activity versus apnea (like theophylline), but which may have toxicity when it is not readily metabolized by the liver, and its elimination is slowed by immature kidneys. ... 

Caffeine is rapidly absorbed after an oral dose, with peak levels reached within 1-2 h at therapeutic doses. Onset of clinical effects occurs within 60 min. In adults, caffeine is extensively metabolized by the liver primarily by N-demethylation. It is excreted in the urine primarily as 1-methyluric acid and 1-methylxan-thine. Theophylline (1,3-dimethylxanthine) is a minor product of caffeine metabolism in adults (< 1%). After massive caffeine overdoses, serum levels of theophylline are measurable. The elimination half-life of caffeine is 3-6 h at therapeutic doses. The half-life is shorter in smokers and is prolonged by oral contraceptives, cimetidine, late pregnancy, and in overdose. The half-life of caffeine is much longer in infants and does not approximate that seen in adults until 6 months of age. The half-life of caffeine may exceed 100 h in preterm infants. Only 1-10% of caffeine appears unchanged in the urine in adults. Neonates may excrete up to 85% of caffeine unchanged. 

Elimination of many drugs (eg, acetaminophen, many antibiotics, caffeine, lidocaine, morphine, phenytoln, and theophylline) is prolonged in neonates. For example, the half-life of caffeine Is approximately 3 hours in adults but may be greater than 100 hours In newborns. 

The elimination of caffeine is impaired in neonates because of their immature metabolizing hepatic enzyme systems. For example, plasma half-lives of 65-103 h in neonates have been reported compared to 3-6 h in adults and the elderly. 

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