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Drug

D0442 | pravastatin

Molecular Formula C23H36O7
Molecular Weight 424.5
Structure
State solid
Clearance The reported clearance rate of pravastatin ranges from 6.3-13.5 ml.min/kg in adults[A177913] while in children it has been reported to be of 4-11 L/min.[A177907]
Volume of distribution The reported steady-state volume of distribution of pravastatin is reported to be of 0.5 L/kg.[A177913] This pharmacokinetic parameter in children was found to range from 31-37 ml/kg.[A177907]
Route of elimination From the administered dose of pravastatin, about 70% is eliminated in the feces while about 20% is obtained in the urine.[T357] When pravastatin is administered intravenously, approximately 47% of the administered dose is eliminated via the urine with 53% of the dose eliminated either via biotransformation of biliary.[F4603]
Protein binding Due its polarity, pravastatin binding to plasma proteins is very limited and the bound form represents only about 43-48% of the administered dose. However, the activity of p-glycoprotein in luminal apical cells and OATP1B1 produce significant changes to pravastatin distribution and elimination.[A177682]
Half life The reported elimination half-life of pravastatin is reported to be of 1.8 hours.[A34502]
Absorption Pravastatin is absorbed 60-90 min after oral administration and it presents a low bioavailability of 17%.[A34502] This low bioavailability can be presented due to the polar nature of pravastatin which produces a high range of first-pass metabolism and incomplete absorption.[T239] Pravastatin is rapidly absorbed from the upper part of the small intestine via proton-coupled carrier-mediated transport to be later taken up in the livery by the sodium-independent bile acid transporter.[A39676] The reported time to reach the peak serum concentration in the range of 30-55 mcg/L is of 1-1.5 hours with an AUC ranging from 60-90 mcg.h/L.[A177907]
Trade names Pravachol, Selektine
Description statin; 6-alpha-hydroxy acid form of mevastatin; inhibitor of HMG-CoA reductase

C

C10BX02 Pravastatin and acetylsalicylic acid


[C10BX] HMG CoA reductase inhibitors, other combinations


[C10B] LIPID MODIFYING AGENTS, COMBINATIONS


[C10] LIPID MODIFYING AGENTS


[C] Cardiovascular system

C10BA03 Pravastatin and fenofibrate


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


[C10B] LIPID MODIFYING AGENTS, COMBINATIONS


[C10] LIPID MODIFYING AGENTS


[C] Cardiovascular system

C10AA03 Pravastatin


[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) >100 1 hour Human HepG2 High-content screening assay Negative MEC 306
MEMBRANE POTENTIAL > 200 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 Negative MEC 306
RESPIRATION 5 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 ND 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. Negative EC20 36
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex I activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex IV activity Negative p < 0.05 3
ELECTRON TRANSPORT CHAIN 50 μM bovine heart mitochondria Measurement of complex V activity Negative p < 0.05 3
SWELLING > 200 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 50 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 50 μM bovine heart mitochondria Measurement of complex I activity Negative p < 0.05 3
NADH:ubiquinone reductase 5 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 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
Succinate dehydrogenase ND 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. Negative EC20 36
Quinol--cytochrome-c reductase 50 μM bovine heart mitochondria Measurement of complex II + III activity Negative p < 0.05 3
Cytochrome c oxidase 50 μM bovine heart mitochondria Measurement of complex IV activity Negative p < 0.05 3
ATP synthase 50 μM bovine heart mitochondria Measurement of complex V activity Negative p < 0.05 3
Reactive oxygen species 50 µM 1 hour Human HepG2 High-content screening assay increase MEC 306
Cytochrome c > 200 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 9 companies from 1 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.


H228 (100%): Flammable solid [Danger Flammable solids]


H314 (100%): Causes severe skin burns and eye damage [Danger Skin corrosion/irritation]


H411 (100%): Toxic to aquatic life with long lasting effects [Hazardous to the aquatic environment, long-term hazard]


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.


 P210, P240, P241, P260, P264, P273, P280, P301+P330+P331, P303+P361+P353, P304+P340, P305+P351+P338, P310, P321, P363, P370+P378, P391, 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
rat LD50 subcutaneous 3172mg/kg (3172mg/kg) Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 15, Pg. 4949, 1987.
mouse LD50 oral 8939mg/kg (8939mg/kg) Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 15, Pg. 4949, 1987.
women TDLo oral 30mg/kg/21W-I (30mg/kg) New England Journal of Medicine. Vol. 327, Pg. 649, 1992.
rat LD50 oral > 12gm/kg (12000mg/kg) Yakkyoku. Pharmacy. Vol. 40, Pg. 2351, 1989.
man TDLo oral 16mg/kg/8W-I (16mg/kg) American Journal of Emergency Medicine. Vol. 17, Pg. 1388, 1999.
mouse LD50 subcutaneous 2975mg/kg (2975mg/kg) Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 15, Pg. 4949, 1987.
rat LDLo intraperitoneal 400mg/kg (400mg/kg) Biochemistry and Molecular Biology International. Vol. 47, Pg. 519, 1999.
mouse LD50 intravenous 2011mg/kg (2011mg/kg) Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 15, Pg. 4949, 1987.
women TDLo oral 16800ug/kg (16.8mg/kg) behavioral: somnolence (general depressed activity) Lancet. Vol. 340, Pg. 910, 1992.
rat LD50 intravenous 440mg/kg (440mg/kg) Yakuri to Chiryo. Pharmacology and Therapeutics. Vol. 15, Pg. 4949, 1987.


  • (+)-(3R,5R)-3,5-dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2-methyl-8-{[(S)-2-methylbutyryl]oxy}-1,2,6,7,8,8a-hexahydro-1-naphthyl]heptanoic acid (3R,5R)-3,5-dihydroxy-7-((1S,2S,6S,8S,8aR)-6-hydroxy-2-methyl-8-((S)-2-methylbutanoyloxy)-1,2,6,7,8,8a-hexahydronaphthalen-1-yl)heptanoic acid; (3R,5R)-3,5-dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2-methyl-8-{[(2S)-2-methylbutanoyl]oxy}-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]heptanoic acid
    (3R,5R)-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2-methyl-8-[(2S)-2-methylbutanoyl]oxy-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid (3R,5R)-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2-methyl-8-{[(2S)-2-methylbutanoyl]oxy}-1,2,6,7,8,8a-hexahydronaphthalen-1-yl]-3,5-dihydroxyheptanoic acid 093P370
    1,2,6,7,8,8a-hexahydro-beta,delta,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-, (1S-(1alpha(betaS*,deltaS*),2alpha,6alpha,8beta(R*),8aalpha))-1-Naphthaleneheptanoic acid 1-Naphthaleneheptanoic acid, 1,2,6,7,8,8a-hexahydro-beta,delta,6-trihydroxy-2-methyl-8-((2S)-2-methyl-1-oxobutoxy)-, (betaR,deltaR,1S,2S,6S,8S,8aR)- 1-Naphthaleneheptanoic acid, 1,2,6,7,8,8a-hexahydro-beta,delta,6-trihydroxy-2-methyl-8-(2-methyl-1-oxobutoxy)-, (1S-(1alpha(betas*,deltas*),2alpha,6alpha,8beta(R*),8aalpha))-
    3beta-Hydroxycompactin 81093-37-0 ACT02637
    AKOS015895229 BDBM20688 BIDD:GT0773
    BRD-K60511616-236-01-4 BRD-K60511616-236-02-2 BRD-K60511616-236-08-9
    C-22133 C01844 C10AA03
    C23H36O7 CC-33900 CCG-221195
    CCRIS 7557 CHEBI:63618 CHEMBL1144
    D08410 DB00175 DTXSID6023498
    Eptastatin FT-0082682 GTPL2953
    HMS3715P11 HSDB 8368 HY-B0165
    KS-5015 KXO2KT9N0G LMFA05000695
    LS-94713 Mevalothin NCGC00188962-01
    NCGC00188962-02 PRAVASTATIN SODIUM Pravachol
    Pravastatin (INN) Pravastatin [INN:BAN] Pravastatin acid
    Pravastatin tert-Octylamine Salt Pravastatina Pravastatina [Spanish]
    Pravastatine Pravastatine [French] Pravastatinum
    Pravastatinum [Latin] Pravator (TN) Q1240093
    RMS-431 SC-17346 SCHEMBL1117
    SQ-31,000 SQ-31000 SR-01000781259
    SR-01000781259-2 TUZYXOIXSAXUGO-PZAWKZKUSA-N UNII-KXO2KT9N0G
    ZINC3798763 pravastatin s5713

    DrugBank Name pravastatin
    DrugBank DB00175
    CAS Number 115873-26-2, 81093-37-0
    PubChem Compound 54687
    KEGG Compound ID C01844
    KEGG Drug D08410
    PubChem.Substance 46504851
    ChEBI 20688
    PharmGKB PA451089
    ChemSpider 49398
    BindingDB 20688.0
    TTD DAP000550
    Wikipedia Pravastatin