O Dale1, H Hynne, K Parivar, E Johansson, M Widman. 1. Department of Anesthesia, University Clinic of Trondheim, Norwegian University of Science and Technology, Norway.
Abstract
BACKGROUND: The pharmacokinetics of the steroid anesthetic eltanolone have been studied in male volunteers. However, steroids may exhibit gender-related differences in pharmacokinetics and surgery may alter drug disposition. METHODS: Male (n = 12) and female (n = 9) ASA 1-2 patients (age 26-45 yrs) undergoing discectomy with microsurgical technique were included. Anesthesia was induced with eltanolone 0.75 mg/kg and maintained with nitrous oxide, fentanyl and atracurium. Venous blood was sampled for up to 12 h and analyzed for eltanolone and its major metabolites. RESULTS: Induction was smooth and anesthesia uneventful, except that five cases developed a mild transient erythema. Loss of verbal contact occurred within 20-60 s. Pharmacokinetics in one person deviated significantly from the rest of the subjects. No difference between groups with respect to the primary outcome variable noncompartmental clearance (Cl, 1/min) 1.7 vs 1.6, was found. However, the volume of distribution at steady state (Vss, 1/kg) was larger in women (3.1) compared to men (1.3). The pharmacokinetics followed a three-compartment model. The half-lives (min) of the alpha, beta and gamma phases (men vs women, medians) were 1.5 vs 2.2, 42 vs 40 and 222 vs 360, respectively. Area under the curve (AUC, min microgram/l) was 39,810 vs 34,905. Context-sensitive modelling indicated that it may take 10 min more for women than men to recover from an eltanolone infusion of 2 h duration. CONCLUSION: The gender-related differences in the pharmacokinetics of eltanolone were small, and of little clinical significance for induction of anesthesia with eltanolone.
BACKGROUND: The pharmacokinetics of the steroid anesthetic eltanolone have been studied in male volunteers. However, steroids may exhibit gender-related differences in pharmacokinetics and surgery may alter drug disposition. METHODS: Male (n = 12) and female (n = 9) ASA 1-2 patients (age 26-45 yrs) undergoing discectomy with microsurgical technique were included. Anesthesia was induced with eltanolone 0.75 mg/kg and maintained with nitrous oxide, fentanyl and atracurium. Venous blood was sampled for up to 12 h and analyzed for eltanolone and its major metabolites. RESULTS: Induction was smooth and anesthesia uneventful, except that five cases developed a mild transient erythema. Loss of verbal contact occurred within 20-60 s. Pharmacokinetics in one person deviated significantly from the rest of the subjects. No difference between groups with respect to the primary outcome variable noncompartmental clearance (Cl, 1/min) 1.7 vs 1.6, was found. However, the volume of distribution at steady state (Vss, 1/kg) was larger in women (3.1) compared to men (1.3). The pharmacokinetics followed a three-compartment model. The half-lives (min) of the alpha, beta and gamma phases (men vs women, medians) were 1.5 vs 2.2, 42 vs 40 and 222 vs 360, respectively. Area under the curve (AUC, min microgram/l) was 39,810 vs 34,905. Context-sensitive modelling indicated that it may take 10 min more for women than men to recover from an eltanolone infusion of 2 h duration. CONCLUSION: The gender-related differences in the pharmacokinetics of eltanolone were small, and of little clinical significance for induction of anesthesia with eltanolone.
Authors: Joyce Oi Yan Chan; Marie Moullet; Beth Williamson; Rosalinda H Arends; Venkatesh Pilla Reddy Journal: Front Pharmacol Date: 2022-06-06 Impact factor: 5.988