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- W2029959199 abstract "ABSTRACT: Keto-doxapram (keto-dox), an oxidative metabolite of doxapram, is a possible ventilatory stimulating agent. Our study characterizes its ventilatory properties, pharmacodynamic effects, and pharmacokinetic profile, and those of its parent compound, doxapram. Two groups of five awake, unsedated, newborn lambs (2- to 6-d old) received, respectively, i.v. infusions of keto-dox or doxapram (2.5 mg/kg) over a period of 1 min. Ventilatory parameters were continuously recorded before and for 1 h after the drug infusion. The pharmacokinetic profiles of both drugs were determined from blood samples collected serially before and after drug injection. Both drugs stimulated ventilation. Keto-dox increased baseline minute ventilation by 46 ± 6.1% and 27.8 ± 8.1% (p < 0.002) at 1 and 5 min, respectively, an effect that decreased after 5 min of infusion. Doxapram increased minute ventilation by 57 ± 9% (p < 0.002) at 1 min, and by 48 ± 7% at 5 min, but its effect lasted for 20 min after injection. Compared with the effects of keto-dox, this doxapram increase was significantly higher (p < 0.02). Also, doxapram, but not keto-dox, caused an increase in systolic blood pressure (from 110 ± 3.5 to 118 ± 3.4 mm Hg at 10 min, p < 0.01), as well as a change in neuro-behavior. Both drugs exhibited a biexponential decay curve, characterized by a short alpha and a longer beta t1/2, but keto-dox has a faster elimination rate. These data demonstrate that both doxapram and keto-dox have respiratory-stimulating properties but that only doxapram is associated with adverse effects such as increased blood pressure and agitation. Keto-dox, however, has a shorter beta t1/2 than doxapram. In addition, doxapram is biotransformed to keto-dox, although the converse does not happen. The results suggest that further studies on the use of keto-dox as a therapeutic agent are warranted." @default.
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- W2029959199 date "1990-08-01" @default.
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- W2029959199 title "Pharmacodynamic Effects and Pharmacokinetic Profiles of Keto-Doxapram and Doxapram in Newborn Lambs" @default.
- W2029959199 doi "https://doi.org/10.1203/00006450-199008000-00013" @default.
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