The disposition of intravenous doxapram in man

The pharmacokinetics of intravenous doxapram in healthy individuals is consistent with a 3-compartment open model. Doxapram was administered by bolus injection (1.5 mg/kg^-1) and by intravenous infusion (6.5 mg/kg^-1 for 2 h) to 5 subjects on separate occasions. There was no significant difference in mean terminal plasma half-lives (355 and 448 min) or in mean total body clearances (5.9 and 5.6 ml/min^-1/kg^-1) following i.v. bolus injection or infusion respectively. In 3 subjects plasma doxapram concentrations during and after i.v. infusion agreed with those predicted from pharmacokinetic values obtained from the bolus injection study. Since mean steady-state concentrations (9.9 µg/ml^-1) would be reached only after an extended interval (mean 15.2 h), a variable-rate infusion regimen was calculated to produce and maintain a concentration of 2 µg/ml^-1 from 15-25 min onwards. A regimen in which the infusion rate is reduced step-wise is recommended to achieve early near-constant plasma doxapram concentrations.