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 apnoea. 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) Clb was extremely slow - 8.5 ml/kg/h (+/- 0.4; 5.8-12.2), t1/2 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 Clb, t1/2 and postnatal age in the whole group or in individual infants. Effective plasma concentrations varied over a wide range (12-36 micrograms/ml) and overlapped with subtherapeutic concentrations (less than or equal to 24 micrograms/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.