Oral doxapram for apnea of prematurity: A randomized dosage trial

To determine the feasibility of oral doxapram dosing in very preterm infants.

Phase-two, open-label randomized trial (ACTRN12621001163897) of two oral doxapram regimens for ≥5 days: higher-dose 48 mg/kg, then 24 mg/kg/6 h vs. lower-dose 24 mg/kg, then 12 mg/kg/6 h. Eligibility: born <32 weeks; CPAP ≥8 cmH₂O; caffeine citrate ≥15 mg/kg; significant apnea or desaturation (16 per group).

steady-state doxapram concentration in therapeutic range 1.5-4.0 mg/L, 2-4 h after 4-5^th maintenance dose. Oximetry, gastric ultrasound and clinical assessment performed at baseline, day 2 and 5.

2/16 (13%) infants in the higher-dose and 7/15 (47%) in the lower-dose group achieved steady state doxapram plasma concentrations in therapeutic range. Most infants (88%) in the higher-dose group had concentrations above therapeutic range. By day 5, oral doxapram increased mean SpO₂ and reduced FiO₂, pCO₂, and percentage time SpO₂ <90%.

Oral doxapram is feasible in very preterm infants with improvements in oxygenation and ventilation. Lower doses (12 mg/kg/6 h) are sufficient in most infants.