Pharmacokinetics of eltanolone following bolus injection and constant rate infusion

Abstract

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.

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

“…The total volume of blood drawn did not exceed 170 ml. Serum was prepared and stored as described earlier (2).…”

“…T HE PHARMACOKINETICS of the steroid anesthetic eltanolone 3a-hydroxy-5b-pregnane-20-one) have previously only been studied in male volunteers (1,2); thus they may have limited relevance for patients undergoing surgery (3,4). In these subjects, the pharmacokinetics of eltanolone was best described by a three-compartment model.…”

Enantioselective pharmacokinetics of the enantiomers of clevidipine following intravenous infusion of the racemate in essential hypertensive patients

“…As previously reported for drugs used during anesthesia, the terminal half-life is often of limited value as regards achievement of steady-state blood levels during infusion and the duration of the effect postinfusion. 15,25,26 It has been proposed that a more clinically relevant measure of the decline in drug concentration following continuous infusion of drugs exhibiting multiexponentially declining concentration vs. time profiles is the context-sensitive halftime rather than the elimination half-life. 15 The present results confirm that the terminal half-life contributes only slightly to the overall postinfusion decline even when the infusion is prolonged, and that it is incorrect to describe the pharmacokinetics of the drug only by means of the terminal half-life.…”