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Drug

D0467 | lovastatin

Molecular Formula C24H36O5
Molecular Weight 404.5
Structure
State solid
Clearance The clearance rate of lovastatin is reported to be of approximate 650 L/h.[L5293]
Volume of distribution Lovastatin is able to cross the blood-brain barrier and placenta. Its reported volume of distribution is of approximately 5000 L.[L5293]
Route of elimination Lovastatin excretion is reported to be represented of about 10% of urine elimination and 83% of fecal elimination. The elimination through the bile is represented either by the absorbed and unabsorbed drug.[L5284]
Protein binding Lovastatin and its beta-hydroxy acid metabolites are highly protein bound, representing more than 90% of the administered dose.[A174583]
Half life Lovastatin half-life is reported to be of 4.5 hours.[L5284] The elimination half-life of the hydroxy acid form of lovastatin is reported to be of 0.7-3 hours.[A174583]
Absorption Studies suggest that less than 5% of the oral dose reaches the general circulation as active inhibitors and the time to peak serum concentration is 2-4 hours. Lovastatin undergoes extensive first-pass metabolism so the availability of the drug in the system is low and variable.[L5284] The peak concentrations of lovastatin when a dose of 10-40 mg is administered are reported to range from 1.04-4.03 ng/ml and an AUC of 14-53 ng.h/ml. This indicates that lovastatin presents a dose-dependent pharmacokinetic profile.[A174586]
Trade names Mevacor
Description statin; treat high blood cholesterol; lipid-lowering drug and fungal metabolite; competitively inhibit the enzyme hydroxymethylglutaryl-coenzyme A (HMG-CoA) Reductase

C

C10BA01 Lovastatin and nicotinic acid


[C10BA] HMG CoA reductase inhibitors in combination with other lipid modifying agents


[C10B] LIPID MODIFYING AGENTS, COMBINATIONS


[C10] LIPID MODIFYING AGENTS


[C] Cardiovascular system

C10AA02 Lovastatin


[C10AA] HMG CoA reductase inhibitors


[C10A] LIPID MODIFYING AGENTS, PLAIN


[C10] LIPID MODIFYING AGENTS


[C] Cardiovascular system

Toxicity Dose Time Species Model Method Action Positive criterion Reference
OPENING OF PERMEABILITY TRANSITION PORE (PTP) 50 µM 1 hour Human HepG2 High-content screening assay Decrease MEC 306
UNCOUPLING increase 36
MEMBRANE POTENTIAL 43.6 µM 30 mins mouse liver mitochondria Rh123 fluorescence (excitation 485 nm, emission 535 nm) are recorded using a fluorescence multi-well plate reader (mCICCP (20 µM) treatments was considered as the 100% baseline for ΔΨm loss) decrease EC20 36
MEMBRANE POTENTIAL 100 µM 1 hour Human HepG2 High-content screening assay Decrease MEC 306
RESPIRATION 4.4 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. decrease EC20 36
RESPIRATION 6.2 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. decrease EC20 36
ELECTRON TRANSPORT CHAIN decrease 36
ELECTRON TRANSPORT CHAIN 100uM C2C12 myoblasts measured ubiquinol:cytochrome c oxidoreductase activity in broken C2C12 mitochondria after acute statin exposure at a fixed concentration for all compounds decrease 180
S,N-GLYCEROPHOSPHATE SHUTTLE C2C12 myoblasts affect 180
SWELLING 71.5 µM 30 mins mouse liver mitochondria swelling assay: Absorbance at 545 nm using a fluorescence multi-well plate reader (CaCl2 (50 µM) was considered as the 100% baseline for the swelling ) increase EC20 36
ROS PRODUCTION 10 µM 1 hour Human HepG2 High-content screening assay Increase MEC 306

Target Dose Time Species Model Method Action Positive criterion Reference
NADH:ubiquinone reductase inhibitor 36
NADH:ubiquinone reductase 4.4 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. inhibit EC20 36
Succinate dehydrogenase 6.2 µM 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. inhibit EC20 36
Quinol--cytochrome-c reductase 100uM C2C12 myoblasts measured ubiquinol:cytochrome c oxidoreductase activity in broken C2C12 mitochondria after acute statin exposure at a fixed concentration for all compounds inhibitor 180
Glycerol-3-phosphate dehydrogenase, mitochondrial C2C12 myoblasts inhibitor 180
Reactive oxygen species 10 µM 1 hour Human HepG2 High-content screening assay increase MEC 306
Cytochrome c 118.2 µM 30 mins mouse liver mitochondria Cytochrome c release was evaluated using ELISA kit ( 20 µg/ml Alamethicin was used as 100% baseline) release EC20 36

Pictogram Signal Statements Precautionary Statement Codes
Danger

Aggregated GHS information provided by 142 companies from 13 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 142 companies. For more detailed information, please visit ECHA C&L website


Of the 12 notification(s) provided by 141 of 142 companies with hazard statement code(s):


H302 (31.21%): Harmful if swallowed [Warning Acute toxicity, oral]


H361 (67.38%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]


H372 (24.82%): Causes damage to organs through prolonged or repeated exposure [Danger Specific target organ toxicity, repeated exposure]


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

The GHS information provided by 1 company from 1 notification to the ECHA C&L Inventory.


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


H312 (100%): Harmful in contact with skin [Warning Acute toxicity, dermal]


H332 (100%): Harmful if inhaled [Warning Acute toxicity, inhalation]


 P261, P264, P270, P271, P280, P301+P312, P302+P352, P304+P312, P304+P340, P312, P322, P330, P363, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)
Warning

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


 P264, P270, P301+P312, P330, 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
child TDLo oral 17mg/kg/3W-I (17mg/kg) behavioral: wakefulness Lancet. Vol. 343, Pg. 973, 1994.
man TDLo oral 240mg/kg/60W- (240mg/kg) behavioral: muscle weakness Annals of Pharmacotherpy. Vol. 26, Pg. 190, 1992.
human TDLo oral 8750ug/kg/14D (8.75mg/kg) Clinical Pharmacology and Therapeutics Vol. 50, Pg. 730, 1991.
women TDLo oral 285mg/kg/30W- (285mg/kg) Israel Journal of Medical Sciences. Vol. 28, Pg. 101, 1992.
mouse LD50 oral > 1gm/kg (1000mg/kg) Journal of Antibiotics. Vol. 32, Pg. 852, 1979.


  • (+)-mevinolin (1S,3R,7S,8S,8aR)-1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-(2-(2R,4R)-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl)-1-naphthalenyl (S)-2-methyl-butyrate (1S,3R,7S,8S,8aR)-1,2,3,7,8,8a-Hexahydro-8-(2-((4R,6R)-4-hydroxy-2-oxo-2H-pyran-6-yl)ethyl)-3,7-dimethylnaphtyl(S)-2-methylbutyrat
    (1S,3R,7S,8S,8aR)-8-(2-((2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl)ethyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl (S)-2-methylbutanoate (1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl (2S)-2-methylbutanoate (1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl (2S)-2-methylbutanoate
    (1S-(1alpha(R*),3alpha,7beta,8beta(2S*,4S*),8abeta))-2-Methylbutanoic acid 1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-(2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl)-1-naphthalenyl ester (2S)-(1S,3R,7S,8S,8aR)-1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2-[(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl]ethyl]-1-naphthalenyl-2-methyl butanoate (2S)-2-Methylbutanoic acid (1S,3R,7S,8S,8aR)-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-[(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl]ethyl]-1-naphthalenyl ester
    (2S)-2-methylbutanoic acid [(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxo-2-oxanyl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] ester (S)-((1S,3R,7S,8S,8AR)-8-(2-((2R,4R)-4-HYDROXY-6-OXO-TETRAHYDRO-2H-PYRAN-2-YL)ETHYL)-3,7-DIMETHYL-1,2,3,7,8,8A-HEXAHYDRONAPHTHALEN-1-YL) 2-METHYLBUTANOATE (S)-((1S,3R,7S,8S,8aR)-8-(2-((2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl)ethyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl) 2-methylbutanoate
    (S)-2-Methyl-butyric acid (1S,3R,7S,8S,8aR)-8-[2-((3R,5R)-4-hydroxy-6-oxo-tetrahydro-pyran-2-yl)-ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl ester (S)-2-Methylbutyric acid, 8-ester with (4R,6R)-6-(2-((1S,2S,6R,8S,8aR)-1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-1-naphthyl)ethyl)tetrahydro-4-hydroxy-2H-pyran-2-one 1,2,6,7,8,8a-Hexahydro-beta,delta-dihydroxy-2,6-dimethyl-8-(2-methyl-1-oxobutyoxy)-1-naphthaleneheptanoic acid delta-lactone
    117141-EP2272825A2 117141-EP2298776A1 1S,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl (2S)-2-methylbutanoate
    1cqp 2-Methyl-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1-naphthalenyl ester butanoic acid 28048-EP2269989A1
    28048-EP2270011A1 28048-EP2272825A2 28048-EP2272841A1
    28048-EP2277507A1 28048-EP2277865A1 28048-EP2280006A1
    28048-EP2281813A1 28048-EP2284158A1 28048-EP2286795A1
    28048-EP2287165A2 28048-EP2287166A2 28048-EP2289892A1
    28048-EP2292620A2 28048-EP2295406A1 28048-EP2295409A1
    28048-EP2298742A1 28048-EP2298745A1 28048-EP2298772A1
    28048-EP2298776A1 28048-EP2298779A1 28048-EP2301923A1
    28048-EP2301931A1 28048-EP2301936A1 28048-EP2305648A1
    28048-EP2308839A1 28048-EP2311808A1 28048-EP2311829A1
    28048-EP2314588A1 2beta,6alpha-Dimethyl-8alpha-(2-methyl-1-oxobutoxy)-mevinic acid lactone 330L755
    6 alpha-Methylcompactin 6-Methylcompactin 6-alpha-Methylcompactin
    6alpha-Methylcompactin 74133-25-8 75330-75-5
    8-[2-((2R,4R)-4-hydroxy-6-oxo(2H-3,4,5-trihydropyran-2-yl))ethyl](1S,7S,8S,3R, 8aR)-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthyl (2S)-2-methylbutanoate 96638-EP2287163A1 96638-EP2305678A1
    9LHU78OQFD A838030 AB00052400-17
    AB00052400_18 AB00052400_19 AB0108514
    AC-13961 ACT02620 ACon0_000534
    ACon1_000390 AKOS005267139 ALBB-027272
    ANW-41686 AOB5269 ARONIS24208
    Altocor Altoprev Artein
    BBL024473 BB_NC-01457 BDBM34168
    BG0243 BIDD:GT0749 BIDD:PXR0113
    BPBio1_000519 BRD-K09416995-001-06-8 BRD-K09416995-001-21-7
    BRN 3631989 BSPBio_000471 BSPBio_001265
    BSPBio_003346 Belvas Butanoic acid, 2-methyl-, (1S,3R,7S,8S,8aR)-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-(2-((2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl)-1-naphthalenyl ester, (2S)-
    Butanoic acid, 2-methyl-, (1S,3R,7S,8S,8aR)-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-(2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl)-1-naphthalenyl ester, (2S)- Butanoic acid, 2-methyl-, 1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-(2-(tetrahydro-4-hydroxy-6-- oxo-2H-pyran-2-yl)ethyl)-1-naphthalenyl ester, (1S-(1alpha(R*),3alpha,7beta,8beta(2S*,4S*),8abeta))- Butanoic acid, 2-methyl-, 1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-(2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl)-1-naphthalenyl ester, (1S-(1-alpha-(R*),3-alpha,7-beta,8-beta-(2S*,4S*),8a-beta))-
    Butanoic acid, 2-methyl-, 1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-(2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl)-1-naphthalenyl ester, (1S-(1alpha(R*),3alpha,7beta,8beta(2S*,4S*),8abeta))- Butanoic acid, 2-methyl-,1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-(2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl)-1-naphthalenyl ester,(1S-(1alpha(R*),3alpha,7beta,8beta(2S*,4S*),8abeta)); C-21799
    C07074 C10AA02 C24H36O5
    CAS-75330-75-5 CC-30040 CC-30041
    CCG-39627 CCRIS 8092 CHEBI:40303
    CHEMBL503 CPD000673570 CS-1990
    CTK2H7081 Cholestra Closterol
    Colevix D00359 DB00227
    DSSTox_CID_784 DSSTox_GSID_20784 DSSTox_RID_75788
    DTXSID5020784 DivK1c_001032 EBD2126857
    EC 616-212-7 EN300-52515 G226
    GTPL2739 HMS1569H13 HMS1792O07
    HMS1923O13 HMS1990O07 HMS2089M06
    HMS2093O03 HMS2096H13 HMS2236F07
    HMS3039N16 HMS3259F10 HMS3268C03
    HMS3403O07 HMS3412H19 HMS3676H19
    HMS3713H13 HMS503O05 HSDB 6534
    HY-N0504 Hipolip Hipovastin
    IDI1_001032 J10136 KBio1_001032
    KBio3_002848 KS-1082 KSC377A8D
    L-154803 L0214 LOVALIP
    LS-46359 Lestatin Lipdip
    Lipivas Lipofren Liposcler
    Lovalip Lovalord Lovastatin & Primycin
    Lovastatin (MK-803) Lovastatin (Mevacor) Lovastatin (USP/INN)
    Lovastatin [USAN:BAN:INN] Lovastatin [USAN:USP:INN:BAN] Lovastatin [USAN]
    Lovastatin, 98% Lovastatin,(S) Lovastatina
    Lovastatina [Spanish] Lovastatine Lovastatine [French]
    Lovastatinum Lovastatinum [Latin] Lovasterol
    Lovastin Lozutin MCULE-4740518260
    MCULE-7087866108 MEGxm0_000398 MEVACOR
    MFCD00072164 MK 803 MK-803
    MK-803 ML-530B MLS000069585
    MLS001055358 MLS006011867 MSD 803
    Mevacor Mevacor (TN) Mevinacor
    Mevinolin (lovastatin) Mevinolin from Aspergillus sp., >=98% (HPLC) Mevinolin from Aspergillus sp., powder
    Mevlor Monacolin K Monakolin K
    N1632 NC00713 NCGC00023509-03
    NCGC00023509-04 NCGC00023509-05 NCGC00023509-06
    NCGC00023509-07 NCGC00023509-08 NCGC00023509-09
    NCGC00023509-10 NCGC00023509-11 NCGC00023509-13
    NCGC00023509-14 NCGC00023509-16 NCGC00254157-01
    NCGC00259026-01 NINDS_001032 NSC-633781
    NSC-758662 NSC633781 NSC758662
    Nergadan Opera_ID_1578 PCZOHLXUXFIOCF-BXMDZJJMSA-N
    Paschol Pharmakon1600-01503977 Prestwick0_000516
    Prestwick1_000516 Prestwick2_000516 Prestwick3_000516
    Prestwick_819 Q417740 RTR-031803
    Rextat Rodatin Rovacor
    S-7779 SAM002589904 SAM002589963
    SBB080686 SBI-0051881.P002 SC-11968
    SCHEMBL14227102 SCHEMBL3136 SMR000058779
    SMR000673570 SPBio_002392 SPECTRUM1503977
    SR-01000000123 SR-01000000123-3 SR-05000001880
    SR-05000001880-1 SR-05000001880-2 STK801953
    Simvastatin impurity, lovastatin- Sivlor Spectrum3_001873
    Spectrum5_001294 Taucor Tecnolip
    Teroltrat Tox21_110888 Tox21_110888_1
    Tox21_201475 Tox21_300268 UNII-9LHU78OQFD
    US9115116, lovastatin US9353061, Lovastatina Z1258578375
    ZINC3812841 [(1S,3R,7S,8S,8aR)-3,7-dimethyl-8-[2-[(2R,4R)-4-oxidanyl-6-oxidanylidene-oxan-2-yl]ethyl]-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (2S)-2-methylbutanoate [(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxo-tetrahydropyran-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (2S)-2-methylbutanoate
    [(1S,3R,7S,8S,8aR)-8-[2-[(2R,4R)-4-hydroxy-6-oxooxan-2-yl]ethyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydronaphthalen-1-yl] (2S)-2-methylbutanoate butanoic acid, 2-methyl-, (1S,3R,7S,8S,8aR)-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-[(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl]ethyl]-1-naphthalenyl ester, (2S)- cid_53232
    lovastatin lovastatin-mevacor mevinolin
    s2061

    DrugBank Name lovastatin
    DrugBank DB00227
    CAS Number 74133-25-8, 75330-75-5
    PubChem Compound 53232
    KEGG Compound ID C07074
    KEGG Drug D00359
    ChEBI 40303
    PharmGKB PA450272