Pharmacokinetic aspects of caffeine in premature infants with apnoea

The pharmacokinetics of caffeine was examined in 13 premature infants (gestational age 25-34 weeks, birth weight 920-2060 g, postnatal age 1-42 days) who received the drug for treatment of opnoea. Caffeine (1% aqueous solution) was given i.v. in single doses; guided by the clinical response infants received between one and seven (mean 2.6) doses of 15 mg/kg. Mean (± SE; range) Cl_b was extremely slow - 8.5 ml/kg/h (±0.4; 5.8-12.2), t_1/2 was prolonged - 65.0 h (±3.7; 48.2-87.5 h) and Vd was 0.781/kg (±0.04; 0.47-1.01). No significant correlation was found between Cl_b, t_1/2 and postnatal age in the whole group or in individual infants. Effective plasma concentrations varied over a wide range (12-36 μg/ml) and overlapped with subtherapeutic concentrations (≤24 μg/ml). Single doses of 15 mg/kg i.v. or p.o. prevented apnoea in most cases, if necessary followed by additional doses. Monitoring the blood level of caffeine in infants receiving frequent repeated doses is necessary to prevent toxicity.