Indications
Etodolac is primarily indicated for the acute and long-term management of symptoms associated with osteoarthritis and rheumatoid arthritis. Additionally, it is utilized for the effective management of pain.
Pharmacodynamics
Etodolac functions as an anti-inflammatory agent with both analgesic and antipyretic properties. The drug's therapeutic effects are primarily derived from its inhibition of prostaglandin synthesis, which plays a critical role in mediating fever, pain, swelling, and inflammation. Etodolac is administered as a racemic mixture, with the pharmacologically active S-enantiomer responsible for its effectiveness, while the R-enantiomer is inactive. Importantly, there is no in vivo conversion from the R-form to the S-form.
Absorption
The systemic bioavailability of etodolac is robust, with at least 80% being absorbed following administration in either tablet or capsule form. This strong bioavailability ensures that a significant portion of the active agent is available for therapeutic action.
Metabolism
Etodolac undergoes extensive hepatic metabolism, with renal excretion being the primary elimination route, accounting for 72% of total excretion. In urine, unmetabolized etodolac represents 1% of the administered dose, while etodolac glucuronide accounts for 13%. Hydroxylated metabolites, including 6-, 7-, and 8-hydroxy derivatives, account for 5%, and their corresponding glucuronides contribute 20%. The remaining 33% comprises unidentified metabolites. Fecal excretion represents 16% of the drug's total elimination.
Mechanism of Action
Etodolac exerts its therapeutic effects through the inhibition of the cyclooxygenase (COX) enzyme, a mechanism common to nonsteroidal anti-inflammatory drugs (NSAIDs). This inhibition leads to a decreased synthesis of peripheral prostaglandins, which play a critical role in the inflammatory process. By binding to the upper portion of the COX enzyme's active site, etodolac prevents the substrate, arachidonic acid, from accessing the site, thereby decreasing the enzyme's activity. Initially considered a non-selective COX inhibitor, etodolac is now recognized to be significantly more selective-between 5 to 50 times-for COX-2 over COX-1. Additionally, its antipyretic effects arise from a central action on the hypothalamus, promoting peripheral dilation, which enhances cutaneous blood flow and facilitates heat dissipation.
