Drug
sevoflurane

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PharmGKB has no annotated drug labels with pharmacogenomic information for this . If you know of a drug label with PGx, send us a message.

PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

? = Mouse-over for quick help

The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for sevoflurane

Gene ? Variant?
(144)
Alternate Names ? Drugs ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA
rs112563513 11258081G>A, 38989863G>A, 7007G>A, 70524G>A, Arg2336His
G > A
Missense
Arg2336His
No VIP available CA VA
rs118192122 11259501G>A, 38991283G>A, 71944G>A, 7361G>A, Arg2454His
G > A
Missense
Arg2454His
No VIP available CA No Variant Annotations available
rs118192124 11259494C>T, 38991276C>T, 71937C>T, 7354C>T, Arg2452Trp
C > T
Missense
Arg2452Trp
No VIP available CA VA
rs118192161 11203069C>T, 15512C>T, 38934851C>T, 487C>T, Arg163Cys
C > T
Missense
Arg163Cys
No VIP available CA VA
rs118192162 11214217A>C, 11214217A>G, 1565A>C, 1565A>G, 26660A>C, 26660A>G, 38945999A>C, 38945999A>G, Tyr522Cys, Tyr522Ser
A > C
A > G
Missense
Tyr522Cys
Tyr522Ser
No VIP available CA VA
rs118192163 11253423G>A, 11253423G>C, 38985205G>A, 38985205G>C, 6488G>A, 6488G>C, 65866G>A, 65866G>C, Arg2163His, Arg2163Pro
G > A
G > C
Missense
Arg2163Pro
Arg2163His
No VIP available CA VA
rs118192167 11338862A>G, 14372A>G, 14387A>G, 151305A>G, 39070644A>G, Tyr4791Cys, Tyr4796Cys
A > G
Missense
Tyr4796Cys
No VIP available CA VA
rs118192170 11343847T>C, 14678T>C, 14693T>C, 156290T>C, 39075629T>C, Ile4893Thr, Ile4898Thr
T > C
Missense
Ile4898Thr
No VIP available CA VA
rs118192172 11216403C>T, 1840C>T, 28846C>T, 38948185C>T, Arg614Cys
C > T
Missense
Arg614Cys
No VIP available CA VA
rs118192175 11253422C>T, 38985204C>T, 6487C>T, 65865C>T, Arg2163Cys
C > T
Missense
Arg2163Cys
No VIP available CA VA
rs118192176 11253437G>A, 38985219G>A, 6502G>A, 65880G>A, Val2168Met
G > A
Missense
Val2168Met
No VIP available CA VA
rs118192177 11255141C>G, 11255141C>T, 38986923C>G, 38986923C>T, 6617C>G, 6617C>T, 67584C>G, 67584C>T, Thr2206Arg, Thr2206Met
C > G
C > T
Missense
Thr2206Arg
Thr2206Met
No VIP available CA VA
rs121918592 1021G>A, 1021G>C, 11207570G>A, 11207570G>C, 20013G>A, 20013G>C, 38939352G>A, 38939352G>C, Gly341Arg
G > A
G > C
Missense
Gly341Arg
No VIP available CA VA
rs121918593 11258851G>A, 38990633G>A, 71294G>A, 7300G>A, Gly2434Arg
G > A
Missense
Gly2434Arg
No VIP available CA VA
rs121918594 11259513G>A, 38991295G>A, 71956G>A, 7373G>A, Arg2458His
G > A
Missense
Arg2458His
No VIP available CA VA
rs121918595 11338952C>T, 14462C>T, 14477C>T, 151395C>T, 39070734C>T, Thr4821Ile, Thr4826Ile
C > T
Missense
Thr4826Ile
No VIP available CA No Variant Annotations available
rs1800559 201029943C>T, 3257G>A, 52518585C>T, 56752G>A, Arg1086His
C > T
Missense
Arg1086His
No VIP available CA No Variant Annotations available
rs1801086 11205568G>A, 11205568G>C, 11205568G>M, 18011G>A, 18011G>C, 18011G>M, 38937350G>A, 38937350G>C, 38937350G>M, 742G>A, 742G>C, 742G>M, Gly248Arg, RYR1:ARG248GLY
G > A
G > C
Missense
Gly248Arg
No VIP available CA No Variant Annotations available
rs193922747 103T>C, 11199660T>C, 12103T>C, 38931442T>C, Cys35Arg
T > C
Missense
Cys35Arg
No VIP available CA VA
rs193922772 11216404G>T, 1841G>T, 28847G>T, 38948186G>T, Arg614Leu
G > A
G > T
Missense
Arg614Leu
No VIP available CA VA
rs193922802 11258513G>A, 38990295G>A, 7048G>A, 70956G>A, Ala2350Thr
G > A
Missense
Ala2350Thr
No VIP available CA No Variant Annotations available
rs193922803 11258528C>T, 38990310C>T, 7063C>T, 70971C>T, Arg2355Trp
C > T
Missense
Arg2355Trp
No VIP available No Clinical Annotations available VA
rs193922807 11258589G>C, 38990371G>C, 71032G>C, 7124G>C, Gly2375Ala
G > C
Missense
Gly2375Ala
No VIP available CA VA
rs193922816 11259500C>T, 38991282C>T, 71943C>T, 7360C>T, Arg2454Cys
C > T
Missense
Arg2454Cys
No VIP available CA No Variant Annotations available
rs28933396 11258855G>A, 11258855G>T, 38990637G>A, 38990637G>T, 71298G>A, 71298G>T, 7304G>A, 7304G>T, Arg2435His, Arg2435Leu, RYR1:ARG2434HIS, RYR1:ARG2435HIS, RYR1:ARG2436HIS, p.R2435H
G > A
G > T
Missense
Arg2435Leu
Arg2435His
No VIP available CA VA
rs28933397 11259512C>T, 38991294C>T, 71955C>T, 7372C>T, 7372CT, ARG2458CYS, Arg2458Cys
C > T
Missense
Arg2458Cys
No VIP available CA No Variant Annotations available
rs63749869 11339298G>A, 14567G>A, 14582G>A, 151741G>A, 39071080G>A, Arg4856His, Arg4861His
G > A
Missense
Arg4861His
No VIP available CA No Variant Annotations available
rs772226819 201061121G>A, 201091993G>A, 25574C>T, 520C>T, Arg174Trp
G > A
Missense
Arg174Trp
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 144
2D structure from PubChem
provided by PubChem

Overview

Generic Names
  • Sevofluran
  • Sevoflurano [INN-Spanish]
  • Sevofluranum [INN-Latin]
Trade Names
  • Sevorane
  • Ultane
Brand Mixture Names

PharmGKB Accession Id:
PA451341
Type(s):
Drug

Description

Sevoflurane (2,2,2-trifluoro-1-[trifluoromethyl]ethyl fluoromethyl ether), also called fluoromethyl, is a sweet-smelling, non-flammable, highly fluorinated methyl isopropyl ether used for induction and maintenance of general anesthesia. Together with desflurane, it is replacing isoflurane and halothane in modern anesthesiology. Wikipedia

Source: Drug Bank

Indication

Used for induction and maintenance of general anesthesia in adult and pediatric patients for inpatient and outpatient surgery.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Sevoflurane induces a reduction in junctional conductance by decreasing gap junction channel opening times and increasing gap junction channel closing times. Sevoflurane also activates calcium dependent ATPase in the sarcoplasmic reticulum by increasing the fluidity of the lipid membrane. It also appears to bind the D subunit of ATP synthase and NADH dehydogenase and also binds to the GABA receptor, the large conductance Ca 2+ activated potassium channel, the glutamate receptor, and the glycine receptor.

Source: Drug Bank

Pharmacology

Sevoflurane (also called fluoromethyl) is a halogenated ether used for induction and maintenance of general anesthesia. Together with desflurane, it is replacing isoflurane and halothane in modern anesthesiology. It is often administered in nitrous oxide and pure oxygen. After desflurane it is the volatile anesthetic with the fastest onset and offset. It induces muscle relaxation and reduces pains sensitivity by altering tissue excitability. It does so by decreasing the extent of gap junction mediated cell-cell coupling and altering the activity of the channels that underlie the action potential.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Relatively little biotransformation, only 5% is metabolized by cytochrome P450 CYP2E1 to hexafluoroisopropanol (HFIP) with release of inorganic fluoride and CO2. No other metabolic pathways have been identified for sevoflurane.

Source: Drug Bank

Absorption

Rapidly absorbed into circulation via the lungs, however solubility in the blood is low.

Source: Drug Bank

Half-Life

15-23 hours

Source: Drug Bank

Toxicity

LC 50=49881 ppm/hr (rat), LD 50=10.8 g/kg (rat)

Source: Drug Bank

Route of Elimination

The low solubility of sevoflurane facilitates rapid elimination via the lungs. In vivo metabolism studies suggest that approximately 5% of the sevoflurane dose may be metabolized. Up to 3.5% of the sevoflurane dose appears in the urine as inorganic fluoride.

Source: Drug Bank

Chemical Properties

Chemical Formula

C4H3F7O

Source: Drug Bank

Isomeric SMILES

C(OC(C(F)(F)F)C(F)(F)F)F

Source: OpenEye

Canonical SMILES

FCOC(C(F)(F)F)C(F)(F)F

Source: Drug Bank

Average Molecular Weight

200.0548

Source: Drug Bank

Monoisotopic Molecular Weight

200.007212153

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

EvidenceGene
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
CACNA1S
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
RYR1

Drug Targets

Gene Description
ATP2C1 (source: Drug Bank)
ATP5D (source: Drug Bank)
GABRA1 (source: Drug Bank)
GLRA1 (source: Drug Bank)
GRIA1 (source: Drug Bank)
KCNA1 (source: Drug Bank)
MT-ND1 (source: Drug Bank)
No related drugs are available.

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

Induces
Contraindicated With

Publications related to sevoflurane: 27

No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Compound RYR1 heterozygosity resulting in a complex phenotype of malignant hyperthermia susceptibility and a core myopathy. Neuromuscular disorders : NMD. 2015. Kraeva N, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
RYR1-related malignant hyperthermia with marked cerebellar involvement - a paradigm of heat-induced CNS injury?. Neuromuscular disorders : NMD. 2015. Forrest Katharine M L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Functional characterisation of the R2452W ryanodine receptor variant associated with malignant hyperthermia susceptibility. Cell calcium. 2014. Roesl Cornelia, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Next-generation DNA sequencing of a Swedish malignant hyperthermia cohort. Clinical genetics. 2014. Broman M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Functional characterization of 2 known ryanodine receptor mutations causing malignant hyperthermia. Anesthesia and analgesia. 2014. Schiemann Anja H, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Functional and genetic characterization of clinical malignant hyperthermia crises: a multi-centre study. Orphanet journal of rare diseases. 2014. Klingler Werner, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Ryanodine receptor type 1 gene variants in the malignant hyperthermia-susceptible population of the United States. Anesthesia and analgesia. 2013. Brandom Barbara W, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Nonspecific sarcolemmal cation channels are critical for the pathogenesis of malignant hyperthermia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2013. Eltit José M, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Cytochrome P450-mediated drug metabolism in the brain. Journal of psychiatry & neuroscience : JPN. 2012. Miksys Sharon, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A study of a family with the skeletal muscle RYR1 mutation (c.7354C>T) associated with central core myopathy and malignant hyperthermia susceptibility. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia. 2012. Taylor A, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Ryanodine receptor type 1 gene mutations found in the Canadian malignant hyperthermia population. Canadian journal of anaesthesia = Journal canadien d'anesthésie. 2011. Kraeva Natasha, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Novel missense mutations and unexpected multiple changes of RYR1 gene in 75 malignant hyperthermia families. Clinical genetics. 2011. Tammaro A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Polymorphic drug metabolism in anaesthesia. Current drug metabolism. 2009. Restrepo Juan G, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Malignant hyperthermia: a pharmacogenetic disorder. Pharmacogenomics. 2008. Stowell Kathryn M. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Association between GSTP1 gene polymorphism and serum alpha-GST concentrations undergoing sevoflurane anaesthesia. European journal of anaesthesiology. 2008. Kaymak C, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Pharmacologic and functional characterization of malignant hyperthermia in the R163C RyR1 knock-in mouse. Anesthesiology. 2006. Yang Tianzhong, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Heat- and anesthesia-induced malignant hyperthermia in an RyR1 knock-in mouse. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2006. Chelu Mihail G, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Malignant hyperthermia in North America: genetic screening of the three hot spots in the type I ryanodine receptor gene. Anesthesiology. 2004. Sei Yoshitatsu, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Patients with malignant hyperthermia demonstrate an altered calcium control mechanism in B lymphocytes. Anesthesiology. 2002. Sei Yoshitatsu, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Increased sensitivity to 4-chloro-m-cresol and caffeine in primary myotubes from malignant hyperthermia susceptible individuals carrying the ryanodine receptor 1 Thr2206Met (C6617T) mutation. Clinical genetics. 2002. Wehner M, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
RYR1 mutations causing central core disease are associated with more severe malignant hyperthermia in vitro contracture test phenotypes. Human mutation. 2002. Robinson Rachel L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Identification of the Arg1086His mutation in the alpha subunit of the voltage-dependent calcium channel (CACNA1S) in a North American family with malignant hyperthermia. Clinical genetics. 2001. Stewart S L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A novel ryanodine receptor mutation and genotype-phenotype correlation in a large malignant hyperthermia New Zealand Maori pedigree. Human molecular genetics. 2000. Brown R L, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Malignant hyperthermia in infancy and identification of novel RYR1 mutation. British journal of anaesthesia. 2000. Chamley D, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Malignant-hyperthermia susceptibility is associated with a mutation of the alpha 1-subunit of the human dihydropyridine-sensitive L-type voltage-dependent calcium-channel receptor in skeletal muscle. American journal of human genetics. 1997. Monnier N, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
Polymorphisms and deduced amino acid substitutions in the coding sequence of the ryanodine receptor (RYR1) gene in individuals with malignant hyperthermia. Genomics. 1992. Gillard E F, et al. PubMed
No Dosing Guideline available No Drug Label available CA No Variant Annotation available No VIP available No VIP available
A substitution of cysteine for arginine 614 in the ryanodine receptor is potentially causative of human malignant hyperthermia. Genomics. 1991. Gillard E F, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0074-4456-04
DrugBank:
DB01236
ChEBI:
9130
KEGG Compound:
C07520
KEGG Drug:
D00547
PubChem Compound:
5206
PubChem Substance:
46508591
9723
Drugs Product Database (DPD):
2172763
ChemSpider:
5017
Therapeutic Targets Database:
DAP000694
FDA Drug Label at DailyMed:
4c6e76bc-c964-4955-e0a3-511d3386a9cc

Clinical Trials

These are trials that mention sevoflurane and are related to either pharmacogenetics or pharmacogenomics.

No trials found.

Common Searches

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Sources for PharmGKB drug information: DrugBank, Open Eye Scientific Software.