Diclofenac works by inhibiting a specific enzyme in the body. This enzyme, cyclooxygenase, is instrumental in the development of pain. Diclofenac binds to the enzyme and inhibits its function, thereby preventing the synthesis of prostaglandins. Prostaglandins mediate inflammatory processes, which subsequently lead to the development of pain. This results in the analgesic, anti-inflammatory and also antipyretic effect of diclofenac.
Diclofenac is absorbed in the GI tract, but experiences a strong "first-pass effect", which is why only about 60% reaches the bloodstream. For this reason, diclofenac is most commonly applied to the skin, as this circumvents the "first-pass effect". The maximum plasma concentration is reached after 1-2 hours on average. Diclofenac is 99% bound to plasma proteins and is mainly metabolized by the liver. Excretion is 70% by the kidneys and 30% by the stool.
Concomitant administration of other NSAIDs or glucocorticoids may increase the risk of gastrointestinal bleeding. Diclofenac may inhibit the action of diuretics and angiotensin II antagonists. Diclofenac may increase serum levels of lithium, phenytoin and cardiac glycosides.