As an opioid agonist of the agonist type, codeine interacts with particular CNS pain-modulating receptors.

The combination of two medications in LERTUS CD® is justified by the fact that the analgesia it produces as a whole outperforms that of its individual components.

The WHO therefore suggests combining a weak opioid like codeine with an NSAID, in this example diclofenac, given the lack of analgesic effect to an NSAID in mild to moderate pain.

When taken orally, codeine retains at least half of its analgesic effects. When compared to other similar morphine medications, codeine has a higher efficacy via PO due to its reduced first-pass hepatic metabolism.

In the liver, codeine is metabolized after it is absorbed, and the byproducts of this metabolism are eliminated in the urine. Around 10% of the supplied amount is demethylated into morphine, which adds to the analgesic effect of the drug.

A dose of 120 mg of codeine given parenterally has an analgesic effect comparable to 10 mg of morphine.

Codeine phosphate also affects the respiratory system, the cough centre, the release of antidiuretic hormone, the vomiting centre, pupillary constriction, gastric pancreatic and biliary secretion, intestinal motility, bile duct pressure, and the amplitude of ureteral contractions.

When given orally, codeine is quickly absorbed in the intestine and has a 70% bioavailability. In the first hepatic pass, the drug is metabolized via conjugation with glucuronide acid.

After oral dosing for 60 minutes, the plasma concentration reaches its maximum. The medicine is primarily removed in the urine as well as as glucuronide conjugates and an inactive compound.

The feces include trace levels of codeine and its metabolites. The majority of a dose of codeine is excreted in the body within 24 hours, with 5 to 15% of it remaining as unaltered codeine and the rest as the result of codeine and its metabolites being conjugated to glucuronides.

The bioavailability of sodium diclofenac and codeine phosphate in tests involving the ingestion of 1 gastro-resistant tablet containing 50 mg of diclofenac and 50 mg of codeine is 102.5% and 112%, respectively.

These investigations demonstrate that the pharmacokinetics and bioavailability of each medicine alone are not affected by the combination of the two drugs.