Plasma theophylline and caffeine and plasma clearance of theophylline during theophylline treatment in the first year of life

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Abstract
Plasma concentrations of caffeine and theophylline were simultaneously determined in 17 preterm infants after oral administration of aminophylline for treatment of apnoea. The ratio of caffeine/theophylline concentration in plasma increased during the first 2 weeks of treatment, owing to the longer time required for caffeine than for theophylline to reach steady state. The caffeine/theophylline ratio at steady state was 0.57±0.03 (mean±SE). Thus, caffeine contributed significantly to the total methylxanthine load in the infants. The plasma clearance of theophylline was calculated from the plasma steady state concentrations. In 3 preterm infants treated with oral aminophylline, repeated sampling showed an approximately linear increase in clearance with time from 16.8±0.4 (mean±SE) at a postnatal age of 6–11 days to 30.9±2.5 ml/kg/h at 64–69 days. In 1 full-term infant treated with oral theophylline from 3.5 to 11.5 months of age, the plasma clearance of theophylline increased in a roughly linear manner, reaching a plateau of about 100 ml/kg/h at 6–7 months of age. This corresponds to the clearance found in 1–4 year old infants.