Pharmacokinetics of doxapram in idiopathic apnea of prematurity

Pharmacokinetics of doxapram were determined in 13 infants with idiopathic apnea of prematurity uncontrolled by aminophylline and caffeine. Doxapram was maintained for 72-96 h at a constant infusion rate of 2-2.5 mg/kg/h. Plasma doxapram levels were measured by gas liquid chromatography. The infants studied had a birth weight of 1,247 +/- 240 g (mean +/- SD), a gestational age of 29.4 +/- 2 weeks and were 9.9 +/- 6 days old. Steady-state plasma doxapram levels reached by all infants averaged 5.8 +/- 1.8 mg/l. Half-life was 6.6 +/- 5.7 h, plasma clearance 0.44 +/- 0.1 litres/kg/h, and calculated volume of distribution 4 +/- 2.7 litres/kg. Doxapram controlled apnea successfully in 12 of 13 babies. A significant fall in PaCO2 and reduction in the rate of apnea was seen within 6-8 h with corresponding doxapram levels of 3.7 +/- 1.8 mg/l. The factors influencing the pharmacokinetics of doxapram in newborns are presently unknown.