EEG analysis and pharmacodynamic modelling after intravenous bolus injection of eltanolone (pregnanolone).
An intravenous bolus dose of 0.75 mg Kg-1 eltanolone emulsion was administered to 18 unpremedicated ASA I or II patients. In addition to clinical observation and haemodynamic monitoring, EEG power spectrum and median frequency were recorded. Venous blood was collected to establish a concentration-effect relation using the median frequency as a pharmacodynamic parameter for hypnotic effect, and with analysis of data with the sigmoidal Emax model. Emax was determined as the maximal decrease of the median frequency caused by the CNS depressant effect of eltanolone. The results of seven of 15 patients with complete serum and EEG analysis could be described by a sigmoidal curve. The calculated IC50, the serum concentration producing 50% inhibition of Emax, was 0.57 micrograms mL-1. Median frequency occasionally decreased independently of eltanolone serum concentration in seven patients because interference by natural sleep was not prevented before induction or during awakening by setting continuous stimulations. In relation to the peak serum concentration, the decrease in median frequency occurred late in one patient. Nevertheless, the present study provides a preliminary estimation of the IC50 of eltanolone. From the clinical point of view, eltanolone showed satisfactory induction characteristics which warrant further evaluation.
Hering
W
W
Department of Experimental and Clinical Pharmacology and Toxicology, University of Erlangen-Nürnberg, Germany.
Schlecht
R
R
Geisslinger
G
G
Biburger
G
G
Dinkel
M
M
Brune
K
K
Rügheimer
E
E
D000293:Adolescent; D000328:Adult; D000513:Alpha Rhythm / Q000187:drug effects; D018686:Anesthetics, Intravenous / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D003700:Delta Rhythm / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects*; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D013511:Minor Surgical Procedures; D010100:Oxygen / Q000097:blood; D011280:Pregnanolone / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology*; D012815:Signal Processing, Computer-Assisted; D012890:Sleep; D014851:Wakefulness
D018686:Anesthetics, Intravenous; D002492:Central Nervous System Depressants; D006993:Hypnotics and Sedatives; D011280:Pregnanolone; D010100:Oxygen