Tilidine

Tilidine is a synthetic opioid painkiller used to treat moderate to severe pain, both acute and chronic. Tilidine is used in the form of hydrochloride or phosphate salt. Because opioids can be abused as intoxicants and have a high potential for dependence, the dispensing of tilidine is strictly regulated.

Pharmacodynamics

Tilidine itself exerts hardly any analgesic effect. During the first liver passage and the subsequent demethylation (catalysed by enzymes of the CYP450 system) to nortilidine, the active opioid is formed. This binds primarily to the µ-opioid receptor, resulting in the analgesic effect.

Pharmacokinetics

Tilidine is rapidly absorbed after oral administration and is subject to a pronounced first-pass effect. Conversion of tilidine to the more active metabolite nortilidine involves CYP3A4 and CYP2C19. Inhibition of these enzymes may thus alter the efficacy and tolerability profile of tilidine. The analgesic effect occurs after 10-15 minutes. After oral administration of 100 mg tilidine plus 8 mg naloxone, the maximum effect is reached in about 25-50 minutes. The duration of action is reported to be 4-6 hours. The elimination half-life for nortilidine is 3-5 hours. Tilidine is 90% metabolized and excreted renally. The remainder is excreted in the feces.

Drug Interaction

Concomitant use of drugs that are also metabolized by the CYP3A4 and CYP2C19 enzymes may attenuate the effect of tilidine. In addition, the plasma level of the other drug may be increased and reach toxic levels.

Side effects

The most common adverse effects are transient nausea and vomiting, dizziness, drowsiness, fatigue, headache, and nervousness. Less common side effects are: Nausea and vomiting (after repeated use), hallucinations, confusion, euphoria, tremor, increased sweating, diarrhea, and abdominal pain.

Tilidine carries a high potential for abuse and dependence, which is why its dispensing is strictly regulated.

Toxicological data

LD50 (rat, oral): 412 mg-kg-1