Excretion, Distribution, and Metabolism of Doxapram Hydrochloride

Bruce, Robert; Pitts, Jefferson E.; Pinchbeck, F.M.; Newman, Jack

doi:10.1021/jm00326a004

Cited by 41 publications

(9 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Pharmacokinetic studies in dogs and humans demonstrated that blood levels decline rapidly after a single intravenous dose ( Fig. 2) (6,10,45), consistent with the short duration of action reported in CNS Drug Reviews, Vol. 12, No.…”

Section: Metabolismsupporting

confidence: 79%

A New Look at the Respiratory Stimulant Doxapram

2006

View full text Add to dashboard Cite

A number of life-threatening clinical disorders may be amenable to treatment with a drug that can stimulate respiratory drive. These include acute respiratory failure secondary to chronic obstructive pulmonary disease, post-anesthetic respiratory depression, and apnea of prematurity. Doxapram has been available for over forty years for the treatment of these conditions and it has a low side effect profile compared to other available agents. Generally though, the use of doxapram has been limited to these clinical niches involving patients in the intensive care, post-anesthesia care and neonatal intensive care units. Recent basic science studies have made considerable progress in understanding the molecular mechanism of doxapram's respiratory stimulant action. Although it is unlikely that doxapram will undergo a clinical renaissance based on this new understanding, it represents a significant advance in our knowledge of the control of breathing.

show abstract

Section: Metabolismsupporting

confidence: 79%

A New Look at the Respiratory Stimulant Doxapram

2006

View full text Add to dashboard Cite

show abstract

“…This medication has extensive extravascular distribution. Doxapram is found in higher concentrations in fat, liver, pancreas, and adrenal glands in dogs [22]. There is no reported study in newborn ani mals.…”

Section: Resultsmentioning

confidence: 89%

Pharmacokinetics of Doxapram in Idiopathic Apnea of Prematurity

Beaudry

Bradley²,

Gramlich³

et al. 1988

Dev Pharmacol Ther

View full text Add to dashboard Cite

Pharmacokinetics of doxapram were determined in 13 infants with idiopathic apnea of prematurity uncontrolled by aminophylline and caffeine. Doxapram was maintained for 72-96 h at a constant infusion rate of 2-2.5 mg/kg/h. Plasma doxapram levels were measured by gas liquid chromatography. The infants studied had a birth weight of 1,247 ± 240 g (mean ± SD), a gestational age of 29.4 ± 2 weeks and were 9.9 ± 6 days old. Steady-state plasma doxapram levels reached by all infants averaged 5.8 ± 1.8 mg/l. Half-life was 6.6 ± 5.7 h, plasma clearance 0.44 ± 0.1 litres/kg/h, and calculated volume of distribution 4 ± 2.7 litres/kg. Doxapram controlled apnea successfully in 12 of 13 babies. A significant fall in PaCO(2) and reduction in the rate of apnea was seen within 6-8 h with corresponding doxapram levels of 3.7 ± 1.8 mg/l. The factors influencing the pharmacokinetics of doxapram in newborns are presently unknown.

show abstract

“…Early experiments in dogs revealed that doxapram is metabolized very quickly when administered IV (Bruce et al. ). In neonatal calves, doxapram was found to increase ventilation within 30–60 seconds of its administration (Bleul et al.…”

Section: Discussionmentioning

confidence: 99%

“…The profound, short-lived respiratory stimulatory effects observed in the present study were not unexpected. Early experiments in dogs revealed that doxapram is metabolized very quickly when administered IV (Bruce et al 1965). In neonatal calves, doxapram was found to increase ventilation within 30-60 seconds of its administration (Bleul et al 2010;Bleul & Bylang 2012).…”

Section: Discussionmentioning

confidence: 99%

Ampakine CX1942 attenuates opioid-induced respiratory depression and corrects the hypoxaemic effects of etorphine in immobilized goats (Capra hircus)

Haw

Meyer

Greer

et al. 2016

Veterinary Anaesthesia and Analgesia

View full text Add to dashboard Cite

Objectives: To determine whether CX1942 reverses respiratory depression in etorphineimmobilized goats, and to compare its effects with those of doxapram hydrochloride. Study design:A prospective, crossover experimental trial conducted at 1753 m.a.s.l. Animals:Eight adult female Boer goats (Capra hircus) with a mean ± standard deviation mass of 27.1 ± 1.6 kg. Methods:Following immobilization with 0.1 mg kg −1 etorphine, goats received one of doxapram, CX1942 or sterile water intravenously, in random order in three trials. Respiratory rate, ventilation and tidal volume were measured continuously. Arterial blood samples for the determination of PaO 2 , PaCO 2 , pH and SaO 2 were taken 2 minutes before and then at 5 minute intervals after drug administration for 25 minutes.Results: Doxapram corrected etorphine-induced respiratory depression but also led to arousal and hyperventilation at 2 minutes after its administration, as indicated by the low PaCO 2 (27.8 ± 4.5 mmHg) and ventilation of 5.32 ± 5.24 L minute −1 above pre-immobilization values. CX1942 improved respiratory parameters and corrected etorphine's hypoxaemic effects more gradually than did doxapram, with a more sustained improvement in PaO 2 and SaO 2 in comparison with the control trial.Conclusions: CX1942 attenuated opioid-induced respiratory depression and corrected the hypoxaemic effects of etorphine in immobilized goats.Clinical relevance: Ampakines potentially offer advantages over doxapram, a conventional treatment, in reversing etorphine-induced respiratory depression without causing unwanted side effects, particularly arousal, in immobilized animals.2

show abstract

Excretion, Distribution, and Metabolism of Doxapram Hydrochloride

Cited by 41 publications

References 0 publications

A New Look at the Respiratory Stimulant Doxapram

A New Look at the Respiratory Stimulant Doxapram

Pharmacokinetics of Doxapram in Idiopathic Apnea of Prematurity

Ampakine CX1942 attenuates opioid-induced respiratory depression and corrects the hypoxaemic effects of etorphine in immobilized goats (Capra hircus)

Contact Info

Product

Resources

About