CP-16171, piroxicam, is a non-steroidal anti-inflammatory medication that inhibits COX. Its IC50 values for human monocyte COX-1 and COX-2 are 47 and 25 μM, respectively[1]. Piroxicam (CP-16171) (167, 333, 500 μM) reduces the T24 and 5637 cell populations. When coupled with 0.05 μM carboplatin, piroxicam (CP-16171) (500 μM) dramatically lowers the viability of T24 and 5637 cells as well. Additionally, the combination prevents booth cells from expressing Ki-67[3].

In 12 out of 18 dogs, piroxicam (CP-16171) (0.3 mg/kg qd 24-h po) lowers the volume of the tumor. This action is caused by apoptosis induction and a decrease in the concentration of basic fibroblast growth factor in the urine[2].

Absorption, Distribution and Excretion
Well absorbed following oral administration.
Piroxicam and its biotransformation products are excreted in urine and feces, with about twice as much appearing in the urine as in the feces. Approximately 5% of a piroxicam dose is excreted unchanged. However, a substantial portion of piroxicam elimination occurs by hepatic metabolism. Piroxicam is excreted into human milk.
0.14 L/kg

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Metabolism / Metabolites
Renal
Piroxicam has known human metabolites that include 5'-Hydroxypiroxicam.

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Biological Half-Life
30 to 86 hours

Hepatotoxicity
Elevated serum aminotransferase levels have been reported in 3% to 18% of patients taking piroxicam, but symptomatic liver disease with jaundice is rare (estimated at 1 to 5 cases per 100,000 prescriptions). The latency to onset of symptoms of clinically apparent liver injury due to piroxicam is variable from a few days to several months, but is generally within the first 1 to 6 weeks of treatment. The pattern of injury is predominantly cholestatic, although cases presenting with mixed or hepatocellular patterns have been reported (Case 1). Eosinophilia, rash and fever can occur, but are not always present and are usually not prominent. Autoantibodies are rarely found. The injury is usually self-limited and recovery occurs within 1 to 2 months. Rare cases of acute liver failure have been reported.
Likelihood score: B (rare but likely cause of clinically apparent liver injury).

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Effects During Pregnancy and Lactation
◉ Summary of Use during Lactation
Low amounts of piroxicam in milk and failure to detect piroxicam or its metabolites in the urine of 2 older infants indicates that it would not be expected to cause adverse effects in older breastfed infants. Because there is no published experience with piroxicam during breastfeeding in the newborn period, shorter-acting agents may be preferred while nursing a newborn or preterm infant.
◉ Effects in Breastfed Infants
No adverse effects were found in the breastfed infant of a patient receiving 20 mg of piroxicam daily for 4 months starting the 9th month postpartum.
Four infants 3 to 4.5 months of age remained healthy during long-term therapy of their mothers with piroxicam 20 mg daily.
◉ Effects on Lactation and Breastmilk
Relevant published information was not found as of the revision date.

[1]. Cyclooxygenase-1 and cyclooxygenase-2 selectivity of non-steroidal anti-inflammatory drugs: investigation using human peripheral monocytes. J Pharm Pharmacol. 2001 Dec;53(12):1679-85.

[2]. Effects of the cyclooxygenase inhibitor, piroxicam, on tumor response, apoptosis, and angiogenesis in a canine model of human invasive urinary bladder cancer. Cancer Res. 2002 Jan 15;62(2):356-8.

[3]. Synergistic Effect of Carboplatin and Piroxicam on Two Bladder Cancer Cell Lines. Anticancer Res. 2017 Apr;37(4):1737-1745.

Piroxicam is a monocarboxylic acid amide resulting from the formal condensation of the carboxy group of 4-hydroxy-2-methyl-2H-1,2-benzothiazine-3-carboxylic acid 1,1-dioxide with the exocyclic nitrogen of 2-aminopyridine. A non-steroidal anti-inflammatory drug of the oxicam class, it is used to relieve pain and works by preventing the production of endogenous prostaglandins involved in the mediation of pain, stiffness, tenderness and swelling. It has a role as an analgesic, a cyclooxygenase 1 inhibitor, a non-steroidal anti-inflammatory drug, an EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor and an antirheumatic drug. It is a benzothiazine, a member of pyridines and a monocarboxylic acid amide.
A cyclooxygenase inhibiting, non-steroidal anti-inflammatory agent (NSAID) that is well established in treating rheumatoid arthritis and osteoarthritis and used for musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily.
Piroxicam is a Nonsteroidal Anti-inflammatory Drug. The mechanism of action of piroxicam is as a Cyclooxygenase Inhibitor.
Piroxicam is a commonly used nonsteroidal antiinflammatory drug (NSAID) that is available by prescription only and is used in therapy of chronic arthritis. Piroxicam can cause mild serum aminotransferase elevations and, in rare instances, leads to clinically apparent acute liver injury that can be severe and even fatal.
Piroxicam is a nonsteroidal oxicam derivative with anti-inflammatory, antipyretic and analgesic properties. As a non-selective, nonsteroidal anti-inflammatory drug (NSAID), piroxicam binds and chelates both isoforms of cyclooxygenases (COX1 and COX2), thereby stalling phospholipase A2 activity and conversion of arachidonic acid into prostaglandin precursors at the rate limiting cyclooxygenase enzyme step. This results in inhibition of prostaglandin biosynthesis. As a second, independent effect, piroxicam inhibits the activation of neutrophils thereby contributing to its overall anti-inflammatory effects.
A cyclooxygenase inhibiting, non-steroidal anti-inflammatory agent (NSAID) that is well established in treating rheumatoid arthritis and osteoarthritis and used for musculoskeletal disorders, dysmenorrhea, and postoperative pain. Its long half-life enables it to be administered once daily.
See also: Piroxicam Olamine (is active moiety of); Piroxicam betadex (has subclass).

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Drug Indication
For treatment of osteoarthritis and rheumatoid arthritis.
FDA Label

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Mechanism of Action
The antiinflammatory effect of Piroxicam may result from the reversible inhibition of cyclooxygenase, causing the peripheral inhibition of prostaglandin synthesis. The prostaglandins are produced by an enzyme called Cox-1. Piroxicam blocks the Cox-1 enzyme, resulting into the disruption of production of prostaglandins. Piroxicam also inhibits the migration of leukocytes into sites of inflammation and prevents the formation of thromboxane A2, an aggregating agent, by the platelets.

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Pharmacodynamics
Piroxicam is in a class of drugs called nonsteroidal anti-inflammatory drugs (NSAIDs). Piroxicam works by reducing hormones that cause inflammation and pain in the body. Piroxicam is used to reduce the pain, inflammation, and stiffness caused by rheumatoid arthritis and osteoarthritis.

C15H13N3O4S

331.35

331.062

36322-90-4

Piroxicam-d3;942047-64-5;Piroxicam-d4

54676228

Light yellow to yellow solid powder

1.5±0.1 g/cm3

568.5±60.0 °C at 760 mmHg

198-200°C

297.6±32.9 °C

0.0±1.6 mmHg at 25°C

1.692

2.23

2

6

2

23

611

0

QYSPLQLAKJAUJT-UHFFFAOYSA-N

InChI=1S/C15H13N3O4S/c1-18-13(15(20)17-12-8-4-5-9-16-12)14(19)10-6-2-3-7-11(10)23(18,21)22/h2-9,19H,1H3,(H,16,17,20)

4-hydroxy-2-methyl-1,1-dioxo-N-pyridin-2-yl-1λ6,2-benzothiazine-3-carboxamide

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (7.54 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 (7.54 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 (7.54 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.)