Absorption, Distribution and Excretion
Absorbed slowly from the gastrointestinal tract.
DURATION OF RESPONSE IS DIRECTLY PROPORTIONAL TO T/2 OF DRUG IN PLASMA. LARGER INITIAL DOSE (LOADING DOSE) OF DRUG, SOONER DESIRED THERAPEUTIC RESPONSE IS ATTAINED... /ORAL ANTICOAGULANTS/
BOTH ITS ONSET & DURATION OF ACTION ARE SHORTER THAN THOSE OF DICUMAROL & WARFARIN. THERAPEUTICALLY EFFECTIVE PROTHROMBIN TIME IS ATTAINED IN 24 TO 48 HR. AFTER DISCONTINUATION OF MAINTENANCE THERAPY, PROTHROMBIN TIME RETURNS TO NORMAL IN 1 TO 4 DAYS.
WELL ABSORBED FROM GI TRACT...PEAK PROLONGATION OF PROTHROMBIN TIME 18-48 HR, DURATION 1-4 DAYS...CIRCULATING /DRUG/ ALMOST COMPLETELY BOUND TO PLASMA PROTEINS. UPTAKE...BY ERYTHROCYTES IS VARIABLE...DISTRIBUTED TO LIVER, LUNGS, SPLEEN...KIDNEYS /HUMAN, ORAL/

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Metabolism / Metabolites
Hepatic.
Hepatic.
Half Life: 5-10 hours

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Biological Half-Life
5-10 hours

Toxicity Summary
Phenindione inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decresed prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots. (A308)

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Protein Binding
88%

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Toxicity Data
Oral, mouse: LD50 = 175 mg/kg; Oral, rat: LD50 = 163 mg/kg.

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Interactions
HALOPERIDOL WAS FOUND TO REDUCE PROTHROMBIN TIME NORMALLY PRODUCED BY PHENINDIONE.
ACTIVITY OF...INDANDIONE ANTICOAGULANT PHENINDIONE HAVE ALSO BEEN ENHANCED BY C-17-ALKYLATED ANDROGENS.
CORTICOTROPIN & ADRENOCORTICOSTEROIDS HAVE BEEN REPORTED TO CAUSE SEVERE HEMORRHAGE WHEN GIVEN WITH ORAL ANTICOAGULANTS... /ANTICOAGULANTS/
ANTIPYRINE (IN VIVO) & SULFINPYRAZONE (IN VITRO) HAVE BEEN REPORTED TO INTERACT WITH WARFARIN & SHOULD BE USED CAUTIOUSLY IN PT RECEIVING ANTICOAGULANTS. /ANTICOAGULANTS/
For more Interactions (Complete) data for PHENINDIONE (12 total), please visit the HSDB record page.

Phenindione is a beta-diketone and an aromatic ketone. It has a role as an anticoagulant. It derives from a hydride of an indane.
An indandione that has been used as an anticoagulant. Phenindione has actions similar to warfarin, but it is now rarely employed because of its higher incidence of severe adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p234)
Phenindione is only found in individuals that have used or taken this drug. It is an indandione that has been used as an anticoagulant. Phenindione has actions similar to warfarin, but it is now rarely employed because of its higher incidence of severe adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p234). Phenindione inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.
An indandione that has been used as an anticoagulant. Phenindione has actions similar to WARFARIN, but it is now rarely employed because of its higher incidence of severe adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p234)

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Drug Indication
For the treatment of pulmonary embolism, cardiomyopathy, atrial fibrillation and flutter, cerebral embolism, mural thrombosis, and thrombophili. Also used for anticoagulant prophylaxis.

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Mechanism of Action
Phenindione inhibits vitamin K reductase, resulting in depletion of the reduced form of vitamin K (vitamin KH2). As vitamin K is a cofactor for the carboxylation of glutamate residues on the N-terminal regions of vitamin K-dependent proteins, this limits the gamma-carboxylation and subsequent activation of the vitamin K-dependent coagulant proteins. The synthesis of vitamin K-dependent coagulation factors II, VII, IX, and X and anticoagulant proteins C and S is inhibited. Depression of three of the four vitamin K-dependent coagulation factors (factors II, VII, and X) results in decreased prothrombin levels and a decrease in the amount of thrombin generated and bound to fibrin. This reduces the thrombogenicity of clots.
.../ANTICOAGULANTS/ BLOCK HEPATIC FORMATION OF FACTORS II, VII, IX, & X BY COMPETITIVELY INHIBITING ACTION OF VITAMIN K. ... COUMARIN ANTICOAGULANTS MAY ALSO AFFECT TRANSPORT OF VITAMIN K TO ITS SITE OF ACTION. /ANTICOAGULANTS/
ORAL ANTICOAGULANTS HAVE ONLY ONE MAJOR PHARMACOLOGICAL EFFECT--INHIBITION OF BLOOD-CLOTTING MECHANISMS BY INTERFERING WITH HEPATIC SYNTH OF VITAMIN K-DEPENDENT CLOTTING FACTORS. ...EXERT THEIR INITIAL EFFECT IN VIVO ONLY AFTER LATENT PERIOD... /ORAL ANTICOAGULANTS/

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Therapeutic Uses
Anticoagulants
...ORAL ANTICOAGULANTS ARE USEFUL IN PREVENTION & TREATMENT OF VARIETY OF THROMBOEMBOLIC DISORDERS. /ORAL ANTICOAGULANTS/
...INDICATIONS FOR ANTICOAGULANTS...1) MYOCARDIAL INFARCTION, 2) RHEUMATIC HEART DISEASE, 3) CEREBROVASCULAR DISEASE, 4) VENOUS THROMBOSIS & PULMONARY EMBOLISM, & 5) DISSEMINATED INTRAVASCULAR COAGULATION. /ANTICOAGULANTS/

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Drug Warnings
IT IS INADVISABLE TO CARRY OUT LONG-TERM THERAPY IN CHRONIC ALCOHOLIC, IN INDIVIDUAL WHO MAY REQUIRE INTENSIVE SALICYLATE THERAPY, OR IN CASES OF MALIGNANT HYPERTENSION & ACTIVE TUBERCULOSIS. ORAL ANTICOAGULANT THERAPY DURING PREGNANCY CARRIES SIGNIFICANT HEMORRHAGIC RISK FOR FETUS. /ORAL ANTICOAGULANTS/
...CONTRAINDICATED IN HEMORRHAGIC TENDENCIES, BLOOD DYSCRASIAS, ULCERATIVE LESIONS OF GI TRACT, DIVERTICULITIS, COLITIS, SUBACUTE BACTERIAL ENDOCARDITIS, THREATENED ABORTION, RECENT OPERATIONS ON BRAIN OR SPINAL CORD. REGIONAL & LUMBAR-BLOCK ANESTHESIA, VITAMIN K DEFICIENCY...HEPATIC OR RENAL DISEASE. /ORAL ANTICOAGULANTS/
CHANGES IN AVAIL OF VITAMIN K ALTER THERAPEUTIC RESPONSE TO ORAL ANTICOAGULANTS. ... NEWBORN ARE PARTICULARLY SENSITIVE TO ORAL ANTICOAGULANTS. ... RENAL INSUFFICIENCY, FEVER, & SCURVY ENHANCE OR PROLONG ORAL ANTICOAGULANT RESPONSE. /ORAL ANTICOAGULANTS/
IT CANNOT BE EMPHASIZED TOO STRONGLY THAT TREATMENT OF EACH PT IS HIGHLY INDIVIDUALIZED MATTER. PT ON ANTICOAGULANT THERAPY MUST BE FOLLOWED BY MEANS OF PROTHROMBIN TIME TESTS & OBSERVED CAREFULLY FOR ANY DEVELOPMENT OF BLEEDING TENDENCY. /ANTICOAGULANTS/
For more Drug Warnings (Complete) data for PHENINDIONE (15 total), please visit the HSDB record page.

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Pharmacodynamics
Phenindione thins the blood by antagonizing vitamin K which is required for the production of clotting factors in the liver. Anticoagulants such as Phenindione have no direct effect on an established thrombus, nor do they reverse ischemic tissue damage (damage caused by an inadequate blood supply to an organ or part of the body). However, once a thrombus has occurred, the goal of anticoagulant treatment is to prevent further extension of the formed clot and prevent secondary thromboembolic complications which may result in serious and possibly fatal sequelae. Phenindione has actions similar to warfarin, but it is now rarely employed because of its higer incidence of severe adverse effects.

C15H10O2

222.24

222.068

83-12-5

Phenindione-d5;70711-53-4

4760

LEAFLETS FROM ALCOHOL
CREAMY WHITE TO PALE YELLOW CRYSTALS OR CRYSTALLINE POWDER

1.343g/cm3

243.3 °C (0.3 mmHg)

144-148 °C(lit.)

208 °C

1.703

2.849

0

2

1

17

304

0

O=C1C(C2C=CC=CC=2)C(=O)C2C1=CC=CC=2

NFBAXHOPROOJAW-UHFFFAOYSA-N

InChI=1S/C15H10O2/c16-14-11-8-4-5-9-12(11)15(17)13(14)10-6-2-1-3-7-10/h1-9,13H

2-phenylindene-1,3-dione

Phenylindanedione; 2-Phenyl-1,3-indandione; Phenindione

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ≥ 100 mg/mL (~449.96 mM)
H2O : < 0.1 mg/mL

Solubility in Formulation 1: ≥ 2.5 mg/mL (11.25 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: ≥ 2.5 mg/mL (11.25 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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 (Please use freshly prepared in vivo formulations for optimal results.)