In Hep3B cells, orphenibuta can improve methotrexate's (MTX) anti-cancer efficacy [1]. Hep3B cells may be cytotoxically affected by co-treatment with oxyphenbutazone (2.5–7.5 µM; 48 hours) and MTX (0.25–1.0 µM) [1]. Liver cells can be repaired by orphenibuta [1].

Combining oxyphenbutazone (70 mg/kg/week; oral; divided into two doses; for 13 weeks) with MTX (5.0 or 2.5 mg/kg/week; intraperitoneally) may have anticancer effects [1].

Cytotoxicity Assay[1]
Cell Types: Hep3B Cell
Tested Concentrations: 2.5 µM, 5 µM, 7.5 µM
Incubation Duration: 48 hrs (hours)
Experimental Results: Enhanced cytotoxicity of MTX.

Animal/Disease Models: Wistar strain albino male rats (5-6 weeks; 150-220 g) [1]
Doses: 70 mg/kg/week (co-treatment with MTX 5.0 or 2.5 mg/kg/week)
Route of Administration: Oral ; once a week; taken in two divided doses; for 13 weeks.
Experimental Results: When combined with MTX, it has potential anti-cancer activity in rats.

Absorption, Distribution and Excretion
...OXYPHENBUTAZONE IS EXTENSIVELY BOUND TO PLASMA PROTEINS & HAS PLASMA HALF-TIME OF SEVERAL DAYS. ...ONLY SLOWLY EXCRETED IN URINE, SINCE BINDING TO PLASMA PROTEIN LIMITS...GLOMERULAR FILTRATION, &...RELATIVELY HIGH PKA, WHICH FAVORS PASSIVE REABSORPTION IN DISTAL TUBULE.

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Metabolism / Metabolites
OXIDN OF PHENYLBUTAZONE DURING CHRONIC DOSING BY MEASURING URINARY EXCRETION OF 3 METABOLITES, OXYPHENBUTAZONE GAMMA-HYDROXYPHENBUTAZONE & P,GAMMA-HYDROXYPHENBUTAZONE DURING INFUSION OF HYDROCORTISONE SODIUM SUCCINATE IS REPORTED.

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Biological Half-Life
IN MAN, OXYPHENBUTAZONE HAS BIOLOGICAL HALF-LIFE OF ABOUT 2 DAYS.

Interactions
SOME TRICYCLIC COMPD HAVE BEEN SHOWN TO DELAY OXYPHENYLBUTAZONE ABSORPTION IN RAT BY INCR GASTRIC EMPTYING TIME.
...OXYPHENBUTAZONE MAY PROLONG PROTHROMBIN TIME IN PT RECEIVING COUMARIN ANTICOAGULANTS CONCOMITANTLY & MAY INCR HYPOGLYCEMIC EFFECT OF INSULIN & ORAL HYPOGLYCEMIC AGENTS.
WHEN OXYPHENBUTAZONE & METHANDROSTENOLONE ARE ADMIN CONCURRENTLY IN HUMANS, SERUM OXYPHENBUTAZONE LEVELS MAY BE ELEVATED. PT TREATED WITH THESE CONCURRENTLY SHOULD BE MONITORED FOR SIGNS OF OXYPHENBUTAZONE-INDUCED ADVERSE EFFECTS.
OXYPHENBUTAZONE ABSORPTION...IS DECR BY DESIPRAMINE.
For more Interactions (Complete) data for OXYPHENBUTAZONE (6 total), please visit the HSDB record page.

[1]. Oxyphenbutazone promotes cytotoxicity in rats and Hep3B cellsvia suppression of PGE2 and deactivation of Wnt/β-catenin signaling pathway. Mol Cell Biochem. 2018 Jul;444(1-2):187-196.

[2]. Nonsteroidal anti-inflammatory drug sensitizes Mycobacterium tuberculosis to endogenous and exogenous antimicrobials. Proc Natl Acad Sci U S A. 2012 Oct 2;109(40):16004-11.

Oxyphenbutazone is a metabolite of phenylbutazone obtained by hydroxylation at position 4 of one of the phenyl rings. Commonly used (as its hydrate) to treat pain, swelling and stiffness associated with arthritis and gout, it was withdrawn from the market 1984 following association with blood dyscrasis and Stevens-Johnson syndrome. It has a role as a non-steroidal anti-inflammatory drug, a non-narcotic analgesic, an antipyretic, a gout suppressant, a drug metabolite, a xenobiotic metabolite, an antineoplastic agent and an antimicrobial agent. It is a member of pyrazolidines and a member of phenols. It is functionally related to a phenylbutazone.
Oxyphenbutazone was withdrawn from the Canadian market in March 1985 due to concerns regarding bone marrow suppression.
A non-steroidal anti-inflammatory drug. Oxyphenbutazone eyedrops have been used abroad in the management of postoperative ocular inflammation, superficial eye injuries, and episcleritis. (From AMA, Drug Evaluations Annual, 1994, p2000) It had been used by mouth in rheumatic disorders such as ankylosing spondylitis, osteoarthritis, and rheumatoid arthritis but such use is no longer considered justified owing to the risk of severe hematological adverse effects. (From Martindale, The Extra Pharmacopoeia, 30th ed, p27)

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Mechanism of Action
...HAS PROMINENT ANTI-INFLAMMATORY EFFECTS IN ANIMALS, & COMPARABLE EFFECTS... IN PT WITH RHEUMATOID ARTHRITIS & RELATED DISORDERS. ...INHIBITS BIOSYNTHESIS OF PROSTAGLANDINS, UNCOUPLES OXIDATIVE PHOSPHORYLATION, & INHIBITS ATP-DEPENDENT BIOSYNTHESIS OF MUCOPOLYSACCHARIDE SULFATES IN CARTILAGE. /PHENYLBUTAZONE/

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Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal; Anti-Inflammatory Agents, Topical
EPISCLERITIS & UVEITIS ASSOC WITH RHEUMATOID ARTHRITIS HAVE SOMETIMES BEEN TREATED SUCCESSFULLY WITH...OXYPHENBUTAZONE.
...HAS MILD URICOSURIC EFFECT IN EXPTL ANIMALS & MAN, PROBABLY ATTRIBUTABLE TO ONE OF ITS METABOLITES.
...HAS MILD URICOSURIC EFFECT IN EXPTL ANIMALS & MAN... URICOSURIC EFFECT RESULTS FROM DIMINISHED TUBULAR REABSORPTION OF URIC ACID. ...CAUSES SIGNIFICANT RETENTION OF SODIUM & CHLORIDE, ACCOMPANIED BY REDN IN URINE VOL... REDUCES UPTAKE OF IODINE BY THYROID GLAND...ALSO INHIBITS ENZYMES OF KREBS CYCLE... /PHENYLBUTAZONE/
For more Therapeutic Uses (Complete) data for OXYPHENBUTAZONE (7 total), please visit the HSDB record page.

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Drug Warnings
...40-YR OLD MAN RECEIVED TOTAL DOSE OF 1 G OXYPHENBUTAZONE OVER APPROX 5 DAYS, 2 MO BEFORE ADMISSION TO HOSPITAL WITH SEVERE ANEMIA & LEUCOCYTOSIS; HE DIED ON THIRD DAY AFTER DEVELOPING THIS CONDITION.
...WHITE-BLOOD CELL DISORDER CONCERNED 47-YR-OLD MAN WHO, 13 MO BEFORE ADMISSION WITH TEMP, HAD BEEN GIVEN 1.9 G OXYPHENBUTAZONE OVER 2-WK PERIOD. ON ADMISSION, HE WAS GIVEN 0.6 G OF DRUG; BLOOD EXAM SHOWED THAT HE HAD LEUKEMIA, OF WHICH HE DIED APPROX 4 MO LATER.
IT SHOULD ALWAYS BE TAKEN IMMEDIATELY AFTER MEALS OR WITH FULL GLASS OF MILK, TO MINIMIZE GASTRIC IRRITATION.
OXYPHENBUTAZONE IS SAID TO CAUSE SOMEWHAT LESS GASTRIC IRRITATION /THAN PHENYLBUTAZONE/. ... IT SHOULD BE TAKEN IN 3 OR 4 DIVIDED PORTIONS AFTER MEALS TO LESSEN GASTRIC IRRITATION.
For more Drug Warnings (Complete) data for OXYPHENBUTAZONE (8 total), please visit the HSDB record page.

C19H20N2O3

324.38

324.147

129-20-4

Oxyphenbutazone monohydrate;7081-38-1;Oxyphenbutazone-d9;1189693-23-9;Oxyphenbutazone-13C6

4641

White to off-white solid powder

1.241g/cm3

485.6ºC at 760mmHg

109-111°C

247.5ºC

4.7E-10mmHg at 25°C

1.61

3.623

1

3

5

24

454

0

HFHZKZSRXITVMK-UHFFFAOYSA-N

InChI=1S/C19H20N2O3/c1-2-3-9-17-18(23)20(14-7-5-4-6-8-14)21(19(17)24)15-10-12-16(22)13-11-15/h4-8,10-13,17,22H,2-3,9H2,1H3

4-butyl-1-(4-hydroxyphenyl)-2-phenylpyrazolidine-3,5-dione

G 29701. Oxyphenbutazone; G29701; G-29701

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 (~308.29 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.71 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 (7.71 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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Solubility in Formulation 3: ≥ 2.5 mg/mL (7.71 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly.

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