Doxapram dosage regimen in apnea of prematurity based on pharmacokinetic data

To 18 premature apneic patients refractory to theophylline, doxapram (0.5-2.5 mg/kg/h) was administered in combination with therapeutic doses of theophylline. Doxapram concentrations in serum were measured 48 h after commencement of the infusion and then in 2-hour intervals during a 6-8 h withdrawal. Total body clearance (dose/Css) of the drug ranged from 0.20 to 0.56 liter/h in 13 patients and 1.14 to 1.75 liter/h in 4 patients suggesting a binomial distribution in the disposition kinetics of the drug. Other pharmacokinetic indices, although variable, did not exhibit binomial distribution. The mean volume of distribution and half-life of doxapram were 7.33 +/- 4.55 liter/kg and 8.17 +/- 4.13 h, respectively. Based on our calculations to accelerate the attainment of a steady-state plasma concentration (Css) of approximately 1.5 mg/l, a loading dose of 5.5 mg/kg and a maintenance dose of 1 mg/kg/h along with serum concentration monitoring are recommended.