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Drug

D0052 | Etoposide

Molecular Formula C29H32O13
Molecular Weight 588.6
Structure
State solid
Clearance * Total body clearance = 33 - 48 mL/min [IV administration, adults] * Mean renal clearance = 7 - 10 mL/min/m^2
Volume of distribution The disposition of etoposide is a biphasic process with a distribution half-life of 1.5 hours. It does not cross into cerebrospinal fluid well. Volume of distribution, steady state = 18 - 29 L.
Route of elimination Etoposide is cleared by both renal and nonrenal processes, i.e., metabolism and biliary excretion. Glucuronide and/or sulfate conjugates of etoposide are also excreted in human urine. Biliary excretion of unchanged drug and/or metabolites is an important route of etoposide elimination as fecal recovery of radioactivity is 44% of the intravenous dose. 56% of the dose was in the urine, 45% of which was excreted as etoposide.
Protein binding 97% protein bound.
Half life 4-11 hours
Absorption Absorbed well, time to peak plasma concentration is 1-1.5 hrs. Mean bioavailability is 50% (range of 25% - 75%). Cmax and AUC values for orally administered etoposide capsules display intra- and inter-subject variability. There is no evidence of first-pass effect for etoposide.
Trade names Etopophos
Description inhibits DNA synthesis by forming a complex with topoisomerase II and DNA; derivative of podophyllotoxin

L

L01CB01 Etoposide


[L01CB] Podophyllotoxin derivatives


[L01C] PLANT ALKALOIDS AND OTHER NATURAL PRODUCTS


[L01] ANTINEOPLASTIC AGENTS


[L] Antineoplastic and immunomodulating agents

Toxicity Dose Time Species Model Method Action Positive criterion Reference
OPENING OF PERMEABILITY TRANSITION PORE (PTP) > 100 µM 1 hour Human HepG2 High-content screening assay Negative MEC 306
UNCOUPLING rat isolated liver mitochondria measurements of mitochondrial respiration; RST inhibition assay, RST uncoupling assay; IC 50ratio of glucose/galactose assay Negative 53
MEMBRANE POTENTIAL > 100 µM 1 hour Human HepG2 High-content screening assay Negative MEC 306
ELECTRON TRANSPORT CHAIN rat isolated liver mitochondria measurements of mitochondrial respiration; RST inhibition assay, RST uncoupling assay; IC 50ratio of glucose/galactose assay Negative 53
SWELLING isolated mitochondria increase 57
ROS PRODUCTION > 100 µM 1 hour Human HepG2 High-content screening assay Negative MEC 306
APOPTOSIS isolated mitochondria increase 57

Target Dose Time Species Model Method Action Positive criterion Reference
Reactive oxygen species > 100 µM 1 hour Human HepG2 High-content screening assay Negative MEC 306
Cytochrome c isolated mitochondria release 57

Pictogram Signal Statements Precautionary Statement Codes
Danger

Aggregated GHS information provided by 200 companies from 8 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.


Reported as not meeting GHS hazard criteria by 1 of 200 companies. For more detailed information, please visit ECHA C&L website


Of the 7 notification(s) provided by 199 of 200 companies with hazard statement code(s):


H302 (100%): Harmful if swallowed [Warning Acute toxicity, oral]


H350 (100%): May cause cancer [Danger Carcinogenicity]


Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.


 P201, P202, P264, P270, P281, P301+P312, P308+P313, P330, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)
Danger

H302: Harmful if swallowed [Warning Acute toxicity, oral]


H340: May cause genetic defects [Danger Germ cell mutagenicity]


H350: May cause cancer [Danger Carcinogenicity]


H360: May damage fertility or the unborn child [Danger Reproductive toxicity]


H362: May cause harm to breast-fed children [Reproductive toxicity, effects on or via lactation]


H371: May cause damage to organs [Warning Specific target organ toxicity, single exposure]


H372: Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]


 P201, P202, P260, P263, P264, P270, P281, P301+P312, P308+P313, P309+P311, P314, P330, P405, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

Organism Test type Route Dose (normalized dose) Effect Source
mouse LD50 intravenous 15070ug/kg (15.07mg/kg) National Cancer Institute Screening Program Data Summary, Developmental Therapeutics Program. Vol. JAN1986,
mouse LD50 subcutaneous 143mg/kg (143mg/kg) Drugs in Japan Vol. -, Pg. 190, 1990.
women TDLo intravenous 160ug/kg/3M-C (0.16mg/kg) Lancet. Vol. 341, Pg. 1353, 1993.
rabbit LD50 oral 147mg/kg (147mg/kg) Journal of Toxicological Sciences. Vol. 11(Suppl,
mouse LD50 oral 215mg/kg (215mg/kg) National Cancer Institute Screening Program Data Summary, Developmental Therapeutics Program. Vol. JAN1986,
rat LD50 intravenous 58mg/kg (58mg/kg) Drugs in Japan Vol. -, Pg. 230, 1995.
rat LD50 oral 1784mg/kg (1784mg/kg) Kiso to Rinsho. Clinical Report. Vol. 19, Pg. 3473, 1985.
rat LD50 subcutaneous > 200mg/kg (200mg/kg) Drugs in Japan Vol. -, Pg. 190, 1990.
man TDLo intravenous 57ug/kg/2M-C (0.057mg/kg) Lancet. Vol. 341, Pg. 1353, 1993.
human TDLo intravenous 2630ug/kg/10D (2.63mg/kg) Cancer Vol. 34, Pg. 985, 1974.
mouse LD50 intraperitoneal 64mg/kg (64mg/kg) Kiso to Rinsho. Clinical Report. Vol. 19, Pg. 3473, 1985.
rabbit LD50 intravenous 37mg/kg (37mg/kg) Journal of Toxicological Sciences. Vol. 11(Suppl,
child TDLo intravenous 183mg/kg/2H-C (183mg/kg) behavioral: ataxia Drug Intelligence and Clinical Pharmacy. Vol. 22, Pg. 41, 1988.
rat LD50 intraperitoneal 39mg/kg (39mg/kg) Kiso to Rinsho. Clinical Report. Vol. 19, Pg. 3473, 1985.
human TDLo oral 16mg/kg/5D-I (16mg/kg) Cancer Vol. 34, Pg. 985, 1974.

  • Acquired immunodeficiency syndrome

  • Autoimmune disorder

  • Bladder cancer

  • Brain neoplasm

  • Cervix carcinoma

  • Ewing's sarcoma

  • Gestational trophoblastic tumour

  • Hepatic cancer

  • Hepatic function abnormal

  • Hepatocellular carcinoma

  • Hodgkin's disease

  • Hodgkin's disease lymphocyte depletion type stage unspecified

  • Hodgkin's disease lymphocyte predominance type stage unspecified

  • Hypersensitivity

  • Kaposi's sarcoma

  • Leukaemia

  • Lymphocytic leukaemia

  • Lymphoma

  • Neoplasm

  • Neoplasm malignant

  • Nervous system disorder

  • Neuroblastoma

  • Neutropenia

  • Ovarian cancer

  • Pancytopenia

  • Prostate cancer

  • Renal failure

  • Renal impairment

  • Rhabdomyosarcoma

  • Small cell carcinoma

  • Testicular neoplasm

  • Abdominal pain (0.07)

  • Vomiting (0.37)

  • Asthenia

    • (-)-Etoposide (10R,11R,15R,16S)-16-{[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-hexahydro-2H-pyrano[3,2-d][1,3]dioxin-6-yl]oxy}-10-(4-hydroxy-3,5-dimethoxyphenyl)-4,6,13-trioxatetracyclo[7.7.0.0^{3,7}.0^{11,15}]hexadeca-1(9),2,7-trien-12-one (10r,11r,15r,16s)-16-([(2r,4ar,7r,8r,8as)-7,8-dihydroxy-2-methyl-hexahydro-2h-pyrano[3,2-d][1,3]diox
    (5R,5aR,8aR,9S)-9-(((2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methylhexahydropyrano[3,2-d][1,3]dioxin-6-yl)oxy)-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,5a,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-6(8H)-one (5R,5aR,8aR,9S)-9-(((2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methylhexahydropyrano[3,2-d][1,3]dioxin-6-yl)oxy)-5-(4-hydroxy-3,5-dimethoxyphenyl)-5,8,8a,9-tetrahydrofuro[3',4':6,7]naphtho[2,3-d] (5S,5aR,8aR,9R)-5-[[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-9-(4-hydroxy-3,5-dimethoxy-phenyl)-5a,6,8a,9-tetrahydro-5H-isobenzofuro[5,6-f][1,3]benzodioxol-8-one
    (5S,5aR,8aR,9R)-5-[[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[5,6-f] (5S,5aR,8aR,9R)-5-[[(2R,4aR,6R,7R,8R,8aS)-7,8-dihydroxy-2-methyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-9-(4-hydroxy-3,5-dimethoxyphenyl)-5a,6,8a,9-tetrahydro-5H-[2]benzofuro[6,5-f][1,3]benzodioxol-8-one (5S,5aR,8aR,9R)-9-(4-hydroxy-3,5-dimethoxyphenyl)-8-oxo-5,5a,6,8,8a,9-hexahydrofuro[3'',4'':6,7]naphtho[2,3-d][1,3]dioxol-5-yl 4,6-O-[(1R)-ethylidene]-beta-D-glucopyranoside
    (5S,5aR,8aR,9R)-9-(4-hydroxy-3,5-dimethoxyphenyl)-8-oxo-5,5a,6,8,8a,9-hexahydrofuro[3',4':6,7]naphtho[2,3-d][1,3]dioxol-5-yl 4,6-O-[(1R)-ethylidene]-beta-D-glucopyranoside 13165-EP2269989A1 13165-EP2270008A1
    13165-EP2270014A1 13165-EP2270018A1 13165-EP2272827A1
    13165-EP2272832A1 13165-EP2275413A1 13165-EP2275420A1
    13165-EP2277565A2 13165-EP2277566A2 13165-EP2277567A1
    13165-EP2277568A2 13165-EP2277569A2 13165-EP2277570A2
    13165-EP2277865A1 13165-EP2277876A1 13165-EP2280012A2
    13165-EP2281815A1 13165-EP2287156A1 13165-EP2289892A1
    13165-EP2292280A1 13165-EP2292614A1 13165-EP2292615A1
    13165-EP2292617A1 13165-EP2295055A2 13165-EP2295416A2
    13165-EP2295426A1 13165-EP2295427A1 13165-EP2298305A1
    13165-EP2298746A1 13165-EP2298748A2 13165-EP2298764A1
    13165-EP2298765A1 13165-EP2298768A1 13165-EP2298772A1
    13165-EP2298778A1 13165-EP2298780A1 13165-EP2301928A1
    13165-EP2301933A1 13165-EP2305640A2 13165-EP2305642A2
    13165-EP2305671A1 13165-EP2305679A1 13165-EP2305689A1
    13165-EP2308812A2 13165-EP2308833A2 13165-EP2308839A1
    13165-EP2308855A1 13165-EP2308861A1 13165-EP2311453A1
    13165-EP2311807A1 13165-EP2311808A1 13165-EP2311825A1
    13165-EP2311827A1 13165-EP2311829A1 13165-EP2311840A1
    13165-EP2311842A2 13165-EP2314574A1 13165-EP2316832A1
    13165-EP2316833A1 13165-EP2316834A1 13165-EP2374454A1
    33419-42-0 4''-Demethylepipodophyllotoxin 9-(4,6-O-(R)-ethylidene-beta-D-glucopyranoside) 4'-Demethyl-epipodophyllotoxin 9-[4,6-O-(R)-ethylidene-beta-D-glucopyranoside
    4'-Demethylepipodophyllotoxin 9-(4,6-O-(R)-ethylidene-beta-D-glucopyranoside) 4'-Demethylepipodophyllotoxin 9-(4,6-O-ethylidene-beta-D-glucopyranoside) 4'-Demethylepipodophyllotoxin ethylidene-.beta.-D-glucoside
    4'-O-Demethyl-1-O-(4,6-O-ethylidene-beta-D-glucopyranosyl)epipodophyllotoxin 4-Demethylepipodophyllotoxin beta-D-ethylideneglucoside 419E420
    6PLQ3CP4P3 9-((4,6-O-Ethylidene-beta-D-glucopyranosyl)oxy)-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)-furo(3',4':6,7)naphtho(2,3-d)-1,3-dioxol-6(5aH)-one, (5R-(5alpha,5abeta,8aalpha,9beta(R*)))- 9-((4,6-O-Ethylidine-beta-D-glucopyranosyl)oxy)-5,8,8a,9-tetrahydro-5-(4- hydroxy-3,4-dimethyloxyphenyl)furo (3',4'':6,7) naptho-(2,3-d)-1,3-dioxol-6 (5aH)-one
    9-((4,6-O-Ethylidine-beta-D-glucopyranosyl)oxy)-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,4-dimethyloxyphenyl)furo(3'',4'''':6,7)naptho-(2,3-d)-1,3-dioxol-6(5aH)-one 9-((4,6-O-Ethylidine-beta-D-glucopyranosyl)oxy)-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,4-dimethyloxyphenyl)furo(3',4'':6,7)naptho-(2,3-d)-1,3-dioxol-6(5aH)-one A-8109
    AB00438905 AB00438905-17 AB00438905-18
    AB00438905_19 AB07572 ACN-057122
    AKOS007930275 AS-35312 BCP9000669
    BDBM50127140 BPBio1_000673 BRD-K37798499-001-02-5
    BRD-K37798499-001-05-8 BRD-K37798499-001-10-8 BRD-K37798499-001-14-0
    BRD-K37798499-001-27-2 BSPBio_000611 C-23291
    C01576 C29H32O13 CC-28332
    CCG-101165 CCRIS 2392 CHEBI:4911
    CHEMBL44657 CPD000112002 CS-1774
    D00125 DB00773 Demethyl Epipodophyllotoxin Ethylidine Glucoside
    Demethylepipodophyllotoxin-beta-D-ethylideneglucoside EBD2157958 EINECS 251-509-1
    EVP EX-A1207 Epipodophyllotoxin VP-16213
    Epipodophyllotoxin, 4'-demethyl-, 4,6-O-ethylidene-beta-D-glucopyranoside Epipodophyllotoxin, 4'-demethyl-, 4,6-O-ethylidene-beta-D-glucopyranoside (8CI) Epipodophyllotoxin, 4'-demethyl-, 9-(4,6-O-ethylidene-beta-D-glucopyranoside)
    Epipodophyllotoxin-beta-D-ethyliden-glucoside, 4'-demethyl- Eposide Etopol
    Etopophos (phosphate salt) Etoposide Etoposide (JP17/USP/INN)
    Etoposide (VP-16) Etoposide (VP16) Etoposide [USAN:INN:BAN:JAN]
    Etoposide [USAN:USP:INN:BAN:JAN] Etoposide for system suitability, European Pharmacopoeia (EP) Reference Standard Etoposide, British Pharmacopoeia (BP) Reference Standard
    Etoposide, European Pharmacopoeia (EP) Reference Standard Etoposide, United States Pharmacopeia (USP) Reference Standard Etoposide, synthetic, >=98%, powder
    Etoposide,(S) Etoposido Etoposido [INN-Spanish]
    Etoposidum Etoposidum [INN-Latin] Etosid
    Furo(3',4':6,7)naphtho(2,3-d)-1,3-dioxol-6(5aH)-one, 9-((4,6-O-(1R)-ethylidene-beta-D-glucopyranosyl)oxy)-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)-, (5R,5aR,8aR,9S)- Furo(3',4':6,7)naphtho(2,3-d)-1,3-dioxol-6(5aH)-one, 9-((4,6-O-ethylidene-beta-D-glucopyranosyl)oxy)-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)-, (5R-(5alpha,5abeta,8aalpha,9beta(R*)))- Furo(3',4':6,7)naphtho(2,3-d)-1,3-dioxol-6(5aH)-one-, 9-((4,6-O-ethylidene-beta-D-glucopyranosyl)oxy)5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl), (5R-(5alpha,5abeta,8aalpha,9beta(R*)))-
    Furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6(5aH)-one, 9-[[4,6-O-(1R)-ethylidene-.beta.-D-glucopyranosyl]oxy]-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)-, (5R,5aR,8aR,9S)- GTPL6815 HMS2052N05
    HMS2089F14 HMS2096O13 HMS2232L03
    HMS3713O13 HSDB 6517 HY-13629
    LS-1214 Lastet MFCD00869325
    MLS000049957 MLS001074951 MLS001424283
    MLS002153463 MLS002207239 MLS002222184
    NC00415 NCGC00179504-02 NK 171
    NSC 141540 NSC-141540 NSC141540
    Prestwick3_000396 Q418817 SAM001246880
    SBI-0051910.P002 SCHEMBL4259 SMR000112002
    SR-01000763196 SR-01000763196-3 ST24047199
    Toposar UNII-6PLQ3CP4P3 VJJPUSNTGOMMGY-MRVIYFEKSA-N
    VP 16 VP 16 (pharmaceutical) VP 16-213
    VP 16213 VP-16 VP-16
    VP-16-213 VePESID (TN) VePesid
    Vepesid J Vepeside ZINC3938684
    Zuyeyidal [1,3]benzodioxol-8-one [1,3]dioxol-6(5aH)-one
    [5R-[5?,5a?,8a?,9?(R*)]]-9-[(4,6-?-Ethylidene-?-D-glucopyranosyl)oxy]-5,8,8a,9-tetrahydro-5-(4-hydroxy-3,5-dimethoxyphenyl)furo[3',4':6,7]naphtho[2,3-d]-1,3-dioxol-6-(5aH)-one etoposide s1225
    trans-Etoposide

    DrugBank Name Etoposide
    DrugBank DB00773
    CAS Number 121471-01-0, 33419-42-0, 518-28-5
    PubChem Compound 36462
    KEGG Compound ID C01576
    KEGG Drug D00125
    PubChem.Substance 46505434
    ChEBI 4911
    PharmGKB PA449552
    ChemSpider 33510
    BindingDB 50127140.0
    TTD DAP000786
    Wikipedia Etoposide
    HET EVP
    DPD 1998