Concentration-Effect Relationships of Eltanolone Given as a Bolus Dose or Constant Rate Intravenous Infusion to Healthy Male Volunteers

Wessén, Arne; Parivar, Kourosh; Widman, M; Nilsson, Anders; Hartvig, Per

doi:10.1097/00000542-199606000-00007

Cited by 6 publications

(1 citation statement)

References 18 publications

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“…Analysis of eltanolone, 5b-pregnane-3a,20a-diol and their conjugates was based on gas chromatographic mass spectrometry, as described by Wessén et al (10).…”

mentioning

confidence: 99%

Pharmacokinetics of eltanolone in male and female patients following intravenous bolus injection

Dale

Hynne

Parivar³

et al. 1999

Acta Anaesthesiol Scand

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“…Analysis of eltanolone, 5b-pregnane-3a,20a-diol and their conjugates was based on gas chromatographic mass spectrometry, as described by Wessén et al (10).…”

mentioning

confidence: 99%

Pharmacokinetics of eltanolone in male and female patients following intravenous bolus injection

Dale

Hynne

Parivar³

et al. 1999

Acta Anaesthesiol Scand

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Etomidate and Other Non-Barbiturates

Vanlersberghe¹,

Camu²

Handbook of Experimental Pharmacology

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It is today generally accepted that anesthetics act by binding directly to sensitive target proteins. For certain intravenous anesthetics, such as propofol, barbiturates, and etomidate, the major target for anesthetic effect has been identified as the gamma-aminobutyric acid type A (GABA(A)) receptor, with particular subunits playing a crucial role. Etomidate, an intravenous imidazole general anesthetic, is thought to produce anesthesia by modulating or activating ionotropic Cl(-)-permeable GABA(A) receptors. For the less potent steroid anesthetic agents the picture is less clear, although a relatively small number of targets have been identified as being the most likely candidates. In this review, we summarize the most relevant clinical and experimental pharmacological properties of these intravenous anesthetics, the molecular targets mediating other endpoints of the anesthetic state in vivo, and the work that led to the identification of the GABA(A) receptor as the key target for etomidate and aminosteroids.

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Pharmacokinetics of eltanolone following bolus injection and constant rate infusion

Parivar¹,

Wessén

Widman³

et al. 1996

Journal of Pharmacokinetics and Biopharmaceutics

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Disposition of intravenous anaesthetic eltanolone was studied when administered as a bolus injection (B) of 0.75 mg/kg and constant rate intravenous infusion at 2 mg/kg/hr (12) and 3.5 mg/ kg/hr (13.5) for 2 hr in healthy male volunteers. Venous blood samples were collected for 12 hr and 20 hr following bolus injection and intravenous infusion, respectively. Serum eltanolone concentrations were determined by a specific gas chromatographic mass spectrometric assay. Using a nonlinear regression analysis, the individual data sets were best fitted by a three-compartment mamillary model with central elimination. Derived pharmacokinetic parameters expressed as median and 95% confidence intervals indicated an initial fast distribution with a half-life of 1.80 (0.23-5.47) min (B), 1.44 (0.97-2.06) min (12) and 1.44 (0.95-2.39) min (13.5), an intermediate phase with a half-life of 35.4 (28.7-45.2) min (B), 39.6 (31.0-47.9) min (12) and 35.4 (33.3-44.9) min (13.5) and a moderately short terminal phase with a half-life of 3.8 (2.7-5.9) hr (B), 5.0 (4.2-6.1) hr (12) and 4.6.(4.0-4.8) hr (13.5). The serum clearance after bolus injection was 1.37 (1.23-1.67) L/hr/kg and after infusion was 1.36 (1.25-1.52) L/hr/kg (12) and 1.17 (1.11-1.31) L/hr/kg (13.5). The pharmacokinetics of eltanolone appear to be linear over the dosage range studied. Pharmacokinetic parameters obtained after bolus injection were very much similar to the parameters obtained after infusion with the exception of t1/2 beta which was longer after the infusion (significant) and the volume of central compartment which was lower after infusion (not significant). Context sensitive times were estimated for a 30%, 50% and 80% drop in the concentration of eltanolone after different infusion times. A 30% drop in concentration is estimated to take about 2 to 3 min. A 50% drop in concentration is estimated to take about 8 min when duration of infusion is 3 hr and reaches a value of about 10 min by a duration of infusion of 10 hr. A 80% drop in concentration is estimated to take about 55 min following an infusion of 1 hr and it reaches a value of 70-80 min following an infusion of 10 hr.

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Concentration-Effect Relationships of Eltanolone Given as a Bolus Dose or Constant Rate Intravenous Infusion to Healthy Male Volunteers

Abstract: Recovery characteristics of eltanolone were predictable because of a relatively low interindividual variability in serum concentrations but with a slow blood:effect compartment equilibration.

Cited by 6 publications

References 18 publications

Pharmacokinetics of eltanolone in male and female patients following intravenous bolus injection

Pharmacokinetics of eltanolone in male and female patients following intravenous bolus injection

Etomidate and Other Non-Barbiturates

Pharmacokinetics of eltanolone following bolus injection and constant rate infusion

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