Neonatal theophylline intoxication: pharmacokinetics and clinical evaluation

The pharmacokinetics of theophylline and its metabolites, caffeine, 1,3-dimethyluric acid, 1-methyluric acid and 3-methylxanthine were studied in a 5-day old 1.3 kg premature neonate who accidentally received 180 mg theophylline in 26 h during treatment for bradycardia. Tachycardia, hyperventilation, increased diuresis, central nervous system excitation, an increase in blood glucose concentrations followed by a prolonged decrease and hypercalcaemia were the predominant clinical and laboratory manifestations. The patient responded to supportive care and survived without sequelae. The concentration time course of theophylline and its metabolites in plasma and the pattern of urinary and gastric elimination were determined over 95 h. Theophylline showed, in contrast to its metabolites, a log linear decline in plasma. Elimination of theophylline and caffeine, calculated from their urinary excretion rates, were both exponential during the entire observation period. Urine flow dependence of renal clearance was obvious for theophylline and caffeine. Implications of theophylline disposition in neonates are discussed with special regard to theophylline poisoning.