Pharmacokinetics and pharmacodynamics of eltanolone (pregnanolone), a new steroid intravenous anaesthetic, in humans

@article{Carl1994PharmacokineticsAP,
  title={Pharmacokinetics and pharmacodynamics of eltanolone (pregnanolone), a new steroid intravenous anaesthetic, in humans},
  author={P. Carl and S. H{\o}gskilde and T. Lang-Jensen and V. Bach and J. Jagobsen and M. S{\o}rensen and M. Gr{\"a}lls and L. Widlund},
  journal={Acta Anaesthesiologica Scandinavica},
  year={1994},
  volume={38}
}
Eltanolone, a new intravenous steroid anaesthetic agent was administered intravenously in a dose of 0.6 mg kg‐1 over 45 s to eight healthy male volunteers to evaluate some of its pharmacokinetic and pharmacodynamic effects. Drug concentration–time data were analysed by PCNONLIN, a non–linear regression programme, showing data consistent with a three–compartment model with initial distribution half–life tl/2Xi between 0.3 and 2 min, intermediate distribution half–life 11/22 between 12 and 29 min… Expand
Pharmacokinetics of eltanolone following bolus injection and constant rate infusion
TLDR
The pharmacokinetics of eltanolone appear to be linear over the dosage range studied with the exception of t1/2β which was longer after the infusion (significant) and the volume of central compartment which was lower after infusion (not significant). Expand
Administration to humans of ORG 21465, a water soluble steroid i.v. anaesthetic agent.
TLDR
It is found that ORG 21465 was an effective anaesthetic in humans and the relationship between sedation, anaesthesia and excitation requires further exploration. Expand
Studies of pharmacokinetic and pharmacodynamic properties of isoallopregnanolone in healthy women
TLDR
There was a decrease in saccadic eye movement variables, but no effect was found on self-rated sedation or mood and no changes were seen in prospective symptoms during the menstrual cycle, and no adverse effects were observed after administration of isoallopregnanolone at 0.20 mg/kg. Expand
Safety and clinical effect of i.v. infusion of cyclopropyl‐methoxycarbonyl etomidate (ABP‐700), a soft analogue of etomidate, in healthy subjects
TLDR
Infusions of ABP‐700 showed a dose‐dependent hypnotic effect, and did not cause severe hypotension, severe respiratory depression, or adrenocortical suppression, but the presentation and nature of IMM is a matter of concern. Expand
Myocardial effects of eltanolone in hamsters with hypertrophic cardiomyopathy.
TLDR
Eltanolone is a new short-acting i.v. induction agent that induces less cardiovascular depression than propofol or thiopentone and has no significant effect on intrinsic contractility in normal myocardium, and the effects of eltanolone were not significantly different between normal hamsters and those with cardiomyopathy. Expand
Lack of influence of menstrual cycle and premenstrual syndrome diagnosis on pregnanolone pharmacokinetics
TLDR
Pregnanolone pharmacokinetics do not differ between follicular and luteal phase of the menstrual cycle, nor between PMS patients and control subjects, and no differences in pharmacokinetic variables were detected between cycle phases. Expand
Pharmacokinetic and behavioral effects of allopregnanolone in healthy women
TLDR
The behavioral effects of allopregnanolone are similar to that of its 5β-stereoisomer, pregnanolone, and decreases saccadic eye movement parameters and increases subjective ratings of sedation that correlate with increased serum concentrations of this neuroactive steroid. Expand
Effects of pregnanolone on behavioural parameters and the responses to GABAA receptor antagonists in the late gestation fetal sheep
TLDR
It is concluded that the GABA(A) active steroid pregnanolone suppresses basal and picrotoxin-induced fetal arousal and FBM; and steroid sensitive GABA( A) receptors may regulate fetal behaviour and breathing. Expand
Serum profiles of free and conjugated neuroactive pregnanolone isomers in nonpregnant women of fertile age.
TLDR
The results indicate that a substantial proportion of the progesterone is metabolized in the sequence progester one-->5beta-dihydroprogesterone-->P3alpha5beta-->conjugated P3alpha 5beta, which suggests a gonadal source of PI in the luteal phase. Expand
Anticonflict and Reinforcing Effects of Triazolam + Pregnanolone Combinations in Rhesus Monkeys
TLDR
The results suggest that combinations of triazolam and pregnanolone may have enhanced anxiolytic effects with reduced behavioral disruption and abuse potential compared with either drug alone. Expand
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Pregnanolone emulsion A preliminary pharmacokinetic and pharmacodynamic study of a new intravenous anaesthetic agent
TLDR
Pregnanolone emulsion, a new steroid anaesthetic agent, was administered intravenously as bolus doses to six young healthy male volunteers in a preliminary pharmacokinetic and pharmacodynamic study, finding the pharmacodynamic properties to be similar to those of Althesin. Expand
Pregnanolone emulsion
TLDR
The results indicate that the anaesthetic properties of pregnanolone emulsion are very similar to those of Althesin, and further studies will show whether it can fill the major vacuum left in anaesthetic practice after the withdrawal ofAlthesin. Expand
Pregnanolone: a new steroid intravenous anaesthetic
TLDR
The intravenous steroid anaesthetic pregnanolone has been investigated as an induction agent in 60 fit adults premedicated with morphine and atropine and 31 patients were satisfactorily induced, taking loss of eyelash reflex as the end point. Expand
Pharmacokinetics of propofol in female patients. Studies using single bolus injections.
TLDR
The pharmacokinetics of propofol in a dose of 2.5 mg kg-1 given via a vein in the antecubital fossa were studied in 18 patients and the effects of pretreatment with fentanyl and maintenance with halothane on the pharmacokinetic effects were investigated. Expand
Anaesthetic properties of pregnanolone emulsion
TLDR
The results indicate that pregnanolone emulsion may provide a shortacting, less cumulative and less toxic alternative to existing intravenous anaesthetic agents. Expand
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TLDR
Fentanyl kinetics and excretion in 7 healthy male subjects who were given a 3.2‐ or 6.4‐μg/kg dose of 3H‐fentanyi intravenously and fluctuations in plasma levels may contribute to prolonged and recurrent ventilatory effects of fentanyl. Expand
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Differences in maternal distribution and elimination characteristics of thiopental may be more important determinants of intersubject differences in fetal drug exposure than differences in dose or delta t. Expand
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TLDR
Because of the wide range of safety and minimal respiratory and cardiac depression, hydroxydione has promise of superiority over the ultra-short acting thiobarbiturates for clinical applications in basal or general anesthesia. Expand
Preliminary Study of a Pregnanolone Emulsion (KABI 2213) for I.V. Induction of General Anaesthesia
TLDR
Even if preg-nanolone has all the other desirable attributes of propofol, without rapid reliable emergence, its place in clinical anesthesia will be limited with no great advantages over the present intravenous induction drugs. Expand
Distribution and hepatic metabolism of pregnanolone in the rat.
TLDR
Studies in the rat of pregnanolone, a pharmacologically active metabolite of progesterone, indicated rapid transformation to more polar metabolites, and it was proposed that redistribution rather than hepatic metabolism was the principle mechanism for termination of the hypnotic effect of pregnancy-induced hypnosis. Expand
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