Clinical Pharmacokinetics of Sevoflurane

Abstract

Sevoflurane is a comparatively recent addition to the range of inhalational anaesthetics which has been recently released for clinical use. In comparison to older inhalational agents such as isoflurane or halothane, the most important property of sevoflurane is its low solubility in the blood. This results in a more rapid uptake and induction than the 'older' inhalational agents, improved control of depth of anaesthesia and faster elimination and recovery. The more rapid pharmacokinetics are a result of the low blood/gas partition coefficient of 0.69. With an oil/gas partition coefficient of 47.2, the minimum alveolar concentration (MAC) of sevoflurane is 2.05%. Two to 5% of the drug taken up is metabolised by the liver. The pharmacokinetics of sevoflurane do not change in children, obese patients or patients with renal insufficiency. The pharmacokinetics and pleasant odour of sevoflurane make mask induction feasible, which is an obvious advantage in paediatric anaesthesia. The hepatic metabolism of sevoflurane results in the formation of inorganic fluoride. Upon contact with alkaline CO2 absorbent, a small amount of sevoflurane is degraded and a metabolite (compound A) is formed and inhaled in trace amounts. Whether inorganic fluoride or compound A are nephrotoxic is presently a matter of controversy.

Sevoflurane and isoflurane genotoxicity in kidney cells of mice

“…As known, sevoflurane undergoes much more extensive metabolism than isoflurane (24), which evidently contributed to the amount of reactive compounds with DNA damaging properties. Previous studies suggest that in humans 2-5 % of the absorbed dose of sevoflurane is metabolised, compared to only 0.2 to 2 % of isoflurane (3,25). Second, it is important to mention that sevoflurane biotransformation results in the formation of inorganic fluoride and the so-called compound A, which are both considered toxic and, especially, nephrotoxic (25,26).…”

“…Previous studies suggest that in humans 2-5 % of the absorbed dose of sevoflurane is metabolised, compared to only 0.2 to 2 % of isoflurane (3,25). Second, it is important to mention that sevoflurane biotransformation results in the formation of inorganic fluoride and the so-called compound A, which are both considered toxic and, especially, nephrotoxic (25,26). Goldberg et al (27) found that sevoflurane biotransformation resulted in the generation of greater amounts of fluoride ions than isoflurane.…”

Endocannabinoid signaling in hypothalamic circuits regulates arousal from general anesthesia in mice

“…Sevoflurane-containing gas mixtures (2%) were prepared by delivering the carbogen (95% O 2 /5% CO 2 ) through a calibrated vaporizer. As determined in a recent study (51), the concentration of sevoflurane in the ACSF bubbled with the gas mixtures for >30 minutes was 200 μM, which is the value within the range for clinical and in vivo experimental use (52,53). High-quality polytetrafluorethylene tubing and valves were used to minimize the loss of sevoflurane.…”

The change of sevoflurane to desflurane after anesthesia induction induces rapid emergence without increased cardiovascular responses and emergence delirium in pediatric strabismus surgery patients

“…Rapid inhalation of desflurane does cause cardiovascular changes [6]. The pharmacokinetics and pleasant odor of sevoflurane make mask induction feasible, which is an obvious advantage in pediatric anesthesia [7].…”