title: Solubility of haloether anesthetics in human and animal blood.
abstract: BACKGROUND
  Anesthetic blood solubility predicts pharmacokinetics for inhaled agents and is essential for determination of blood anesthetic concentrations from end-tidal gas concentrations using Henry's Law. Though used to model anesthetic effects in humans, there are limited interspecies solubility comparisons that include modern haloethers. This study aimed to measure hematocrit-adjusted blood:gas anesthetic partition coefficients (λ B:G) for desflurane, sevoflurane, isoflurane, and methoxyflurane in humans and animals.
  
  
  METHODS
  Whole blood was collected from 20 rats, 8 horses, and 4 each of cats, cattle, humans, dogs, goats, pigs, rabbits, and sheep. Plasma or cell volume was removed to adjust all samples to a packed cell volume of 40%. A single-agent calibration gas headspace was added to blood in a glass syringe and was mixed and equilibrated at 37°C for 2 h. Agent concentrations in the calibration gas and syringe headspace were measured using gas chromatography. Anesthetic solubility in saline, citrate-phosphate-dextrose-adenine, and olive oil were similarly measured.
  
  
  RESULTS
  Except for goats, all animal species had at least one λ B:G measurement that differed significantly from humans. For each agent, λ B:G positively correlated with serum triglyceride concentrations, but this only explained 25% of interspecies variability. Desflurane was significantly less soluble in blood than sevoflurane in some species (e.g., humans) but not in others (e.g., rabbits).
  
  
  CONCLUSIONS
  Anesthetic partition coefficients differ significantly between humans and most animals for haloether anesthetics. Because of their similar λ B:G values, goats may be a better animal model for inhaled anesthetic pharmacokinetics in people.
authors.affiliation: Pritchard Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
authors.forename: Joao H N
authors.initials: JH
authors.lastname: Soares
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Brosnan
authors.forename: Fabíola B
authors.initials: FB
authors.lastname: Fukushima
authors.forename: Joanne
authors.initials: J
authors.lastname: Hodges
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
mesh_terms: D000328:Adult; D018685:Anesthetics, Inhalation / Q000737:chemistry*; D000818:Animals; D000077335:Desflurane; D004285:Dogs; D004910:Erythrocyte Membrane / Q000737:chemistry; D006041:Goats; D006801:Humans; D007530:Isoflurane / Q000031:analogs & derivatives / Q000737:chemistry; D008733:Methoxyflurane / Q000737:chemistry; D008738:Methyl Ethers / Q000737:chemistry; D011817:Rabbits; D051381:Rats; D000077149:Sevoflurane; D012756:Sheep; D012995:Solubility; D013552:Swine
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D008733:Methoxyflurane; D000077149:Sevoflurane; D000077335:Desflurane; D007530:Isoflurane