Gastrointestinal absorption of doxapram in neonates

Doxapram was administered orally to six premature babies (3 males, 3 females) with refractory apnea at a mean gestational age of 29 +/- 2.3 weeks, mean birthweight of 1142 +/- 359 gm and a mean postnatal age of 24 days. They received 12, 24, and 36 mg/kg/6 hr on day 1, 2, and 3, respectively, assuming a bioavailability of 50%. Serial plasma doxapram concentrations, determined by high-performance liquid chromatography, increased with incremental doses. The drug underwent oxidative metabolism, producing ketodoxapram, the plasma concentration of which remained stable during treatment. The ratio of plasma concentrations to oral doses ranged from 0.10 to 0.12, suggesting that doxapram is poorly absorbed in the newborn. Oral doxapram may replace the intravenous infusion but doses may have to be increased to, but not exceeding, 24 mg/kg/6 hr to achieve therapeutic plasma concentrations. Interpatient variability, poor absorption and gastrointestinal adverse effects caution against the routine use of oral doxapram.