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Drug

D1274 | ranolazine

Molecular Formula C24H33N3O4
Molecular Weight 427.5
Structure
State solid
Clearance The clearance rate of ranolazine is dose-dependent and the presence of mild-to-moderate renal impairment can increase serum concentration by 40-50%.[A174946] The reported clearance rate of orally administered ranolazine is of 45 L/h when administered a concentration of 500 mg twice daily.[A38645]
Volume of distribution The mean apparent volume of distribution of ranolazine is reported to be of 53.2 L[L5473] and the mean steady-state volume of distribution is of about 180L.[F3616]
Route of elimination From the administered dose, about 75% is excreted renally.[A174898] From this eliminated dose, only about 5% is represented by the unchanged drug.[A174946]
Protein binding In the human body, about 62% of the administered dose of ranolazine is bound to proteins.[A174946] From the studies related to binding in plasma proteins, ranolazine seems to have a higher affinity for alpha-1 acid glycoprotein.[F3616]
Half life Due to the short half-life of the immediate release formulation of ranolazine (1.4-1.9 hours), it was required the generation of an extended-release formulation which presented an approximate steady-state half-life of 7-9 hours.[A174898]
Absorption The time to reach peak serum concentration is very variable but it has been suggested to be of 2-6 hours and to reach steady-state within 3 days.[A174898] The absorption of ranolazine is not modified by food consumption.[A174940] The bioavailability of ranolazine is reported to be of about 73% counting both the unchanged form and the metabolites. After multiple administration of a dose of 500 mg, the reported Cmax and AUC were 1770 ng/ml and 13700 ng.h/ml respectively.[L5473]
Trade names Ranexa
Description partial fatty-acid-oxidation inhibitor (pFOX inhibitor); antianginal drug; metabolic modifier; assumed to be partial FAO inhibitors that targeted 3-ketoacyl-CoA thiolase (3-KAT), a component of the trifunctional protein (TFP) (hydroxyacyl-CoA dehydrogenase/enoyl-CoA hydratase/3-KAT)

C

C01EB18 Ranolazine


[C01EB] Other cardiac preparations


[C01E] OTHER CARDIAC PREPARATIONS


[C01] CARDIAC THERAPY


[C] Cardiovascular system

Toxicity Dose Time Species Model Method Action Positive criterion Reference
GLYCOLYSIS increase 17
FATTY ACID METABOLISM 25μM 24hr T47D cells quantifies the conversion of [9,10-3H(N)]-palmitic acid to 3H2O with diffusion stimulate Student’s two-tail t-test, where p < 0.05 273
MITOCHONDRIAL FATTY ACID BETA OXIDATION decrease 17

Target Dose Time Species Model Method Action Positive criterion Reference
Pyruvate dehydrogenase E1 component subunit alpha, somatic form, mitochondrial 275

Pictogram Signal Statements Precautionary Statement Codes
Danger

Aggregated GHS information provided by 12 companies from 10 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 12 companies. For more detailed information, please visit ECHA C&L website


Of the 9 notification(s) provided by 11 of 12 companies with hazard statement code(s):


H301 (27.27%): Toxic if swallowed [Danger Acute toxicity, oral]


H302 (63.64%): Harmful if swallowed [Warning Acute toxicity, oral]


H315 (36.36%): Causes skin irritation [Warning Skin corrosion/irritation]


H319 (27.27%): Causes serious eye irritation [Warning Serious eye damage/eye irritation]


H335 (36.36%): May cause respiratory irritation [Warning Specific target organ toxicity, single exposure


Respiratory tract irritation]


H336 (18.18%): May cause drowsiness or dizziness [Warning Specific target organ toxicity, single exposure


Narcotic effects]


H361 (27.27%): Suspected of damaging fertility or the unborn child [Warning Reproductive toxicity]


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, P261, P264, P270, P271, P280, P281, P301+P310, P301+P312, P302+P352, P304+P340, P305+P351+P338, P308+P313, P312, P321, P330, P332+P313, P337+P313, P362, P403+P233, 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 subcutaneous > 600mg/kg (600mg/kg) Collection of Czechoslovak Chemical Communications. Vol. 50, Pg. 2289, 1985.
women TDLo oral 150mg/kg (150mg/kg) Acta Medica Scandinavica. Vol. 218, Pg. 525, 1985.
mouse LD50 intravenous 62mg/kg (62mg/kg) United States Patent Document. Vol. #4252984,
mouse LD50 oral 1050mg/kg (1050mg/kg) United States Patent Document. Vol. #4252984,
dog LD50 intravenous 60mg/kg (60mg/kg) Pharmacological and Biochemical Properties of Drug Substances. Vol. 2, Pg. 186, 1979.
rat LD50 oral 3470mg/kg (3470mg/kg) Drugs. International Journal of Current Therapeutics and Applied Pharmacology Reviews. Vol. 14, Pg. 321, 1977.
women TDLo oral 17mg/kg/17D-I (17mg/kg) Annals of Internal Medicine. Vol. 108, Pg. 67, 1988.
mouse LD50 intraperitoneal > 200mg/kg (200mg/kg) Farmaco, Edizione Scientifica. Vol. 41, Pg. 80, 1986.
rat LD50 intravenous 71900ug/kg (71.9mg/kg) Drugs. International Journal of Current Therapeutics and Applied Pharmacology Reviews. Vol. 14, Pg. 321, 1977.


  • antianginal drug assumed to be partial FAO inhibitors that targeted 3-ketoacyl-CoA thiolase (3-KAT), a component of the trifunctional protein (hydroxyacyl-CoA dehydrogenase/enoyl-CoA hydratase/3-KAT) metabolic modifier
    partial fatty-acid-oxidation inhibitor (pFOX inhibitor)

    DrugBank DB00243
    CAS Number 1080496-58-7, 110445-25-5, 142387-99-3, 37350-58-6, 95635-55-5, 95635-56-6
    PubChem Compound 56959