Loxoprofen

246.3

246.30

1806241-263-5

3583H0GZAP

DTXSID1045164

2918300090

54.4

2.4

solid

1.2±0.1 g/cm3

108.5-111 °C

190-195 °C @ Press: 0.3 Torr

220.7±18.3 °C

1.568

47

Keep container tightly closed.

NONH for all modes of transport

3

22-24/25

Stable at normal temperatures and pressures.

Adverse effects include anorexia, nausea, vomiting, bleeding, anemia, diarrhea, and constipation. Loxoprofen toxicity may lead to gastrointestinal disturbance (including flatulence, dyspepsia and gastritis) and renal failure.

99% albumin-bound. At doses of loxoprofen greater than 500 mg/day, clearance of the drug increases as saturation of plasma protein binding occurs at higher doses.

Loxoprofen is non-steroidal anti-inflammatory medication (NSAID) indicated for pain and inflammation related to musculoskeletal and joint disorders. In addition to its effects on pain, it is an antipyretic and anti-inflammatory medication.

Loxoprofen is a non-selective inhibitor of cyclooxygenase enzymes, which are responsible for the formation of various biologically active pain, fever, and inflammatory mediators. These include prostaglandins, prostacyclin, thromboxane, and arachidonic acid.

Anti-inflammatory agents that are non-steroidal in nature. In addition to anti-inflammatory actions, they have analgesic, antipyretic, and platelet-inhibitory actions.They act by blocking the synthesis of prostaglandins by inhibiting cyclooxygenase, which converts arachidonic acid to cyclic endoperoxides, precursors of prostaglandins. Inhibition of prostaglandin synthesis accounts for their analgesic, antipyretic, and platelet-inhibitory actions; other mechanisms may contribute to their anti-inflammatory effects. (See all compounds classified as Anti-Inflammatory Agents, Non-Steroidal.)

Loxoprofen is rapidly and completely absorbed from the GI tract with a bioavailability of 95%. The absorption phase of the medication occurs in the first 4-6 hours after ingestion. Food ingestion with the medication causes a slight decrease in the rate of loxoprofen absorption.|50% renal excretion. This drug is 20% - 30% excreted in the stool.|Loxoprofen has a volume of distribution of 0.16 L/kg.|Most of the drug as unchanged loxoprofen, 6-0-desmethyl loxoprofen (less than 1%) and glucuronide or other conjugates (66-92%). In patients with renal failure, metabolites may accumulate.

Loxoprofen is a prodrug that is rapidly converted to its active trans-alcohol metabolite by carbonyl reductase in the liver. This same process also results in a cis-alcohol metabolite, though this isomer carries little pharmacological activity. The parent drug has also been observed to undergo oxidation via CYP3A4/5 to two hydroxylated metabolites (M3 and M4) and glucuronidation by UGT2B7 to two glucuronide metabolites (M5 and M6). The alcohol metabolites of loxoprofen also undergo glucuronide conjugation via UGT2B7 to two glucuronide metabolites (M7 and M8) prior to excretion. When applied in topical formulations, loxoprofen is metabolized to its active trans-alcohol form by carbonyl reductase in the skin.

The elimination half-life of Loxoprofen is approximately 15 hours. Steady concentration is achieved after 2-3 doses.

Loxoprofen itself is a prodrug and carries little-to-no pharmacological activity - it is rapidly metabolized to its trans-alcohol form, which is a potent and non-selective inhibitor of cyclooxygenase. Cyclooxygenase (COX) is present in 2 forms, COX-1 and COX-2, with each serving different functions. COX-1 is present in human cells and is constitutively released, performing cellular housekeeping functions such as mucus production and platelet aggregation. COX-2 is induced in human cells post-injury or due to other stimuli, is triggered to appear in large quantities at the sites of injury/stimuli, and is ultimately responsible for the mediation of inflammation and pain. Loxoprofen's active metabolite inhibits both COX isoforms, resulting in reduced expression of several mediators of pain, inflammation, and fever (e.g. prostaglandins, prostacyclin, thromboxane, etc).

156-S