Does hydromorphone (Dilaudid) undergo hepatic metabolism?

From the Guidelines

Yes, hydromorphone (Dilaudid) undergoes hepatic metabolism, primarily through glucuronidation, and its metabolites are excreted through the kidneys in urine. According to the most recent and highest quality study, 1, opioids such as hydromorphone should be carefully titrated and frequently monitored for risk or accumulation of the parent drug or active metabolites in patients with hepatic impairment.

Key Points

• Hydromorphone is metabolized in the liver through glucuronidation, which converts the drug into water-soluble compounds that can be eliminated from the body 1.
• The resulting metabolites are primarily excreted through the kidneys in urine, and patients with liver impairment may experience higher blood levels of hydromorphone and increased effects from standard doses 1.
• Healthcare providers typically reduce Dilaudid dosages for patients with hepatic dysfunction to prevent overdosing, and more frequent clinical observation and opioid dose adjustment are recommended for patients with renal or hepatic impairment who receive opioids 1.

Clinical Implications

• Hydromorphone should be used with caution in patients with liver impairment, and its dosage should be adjusted accordingly to prevent overdosing and minimize the risk of adverse effects 1.
• The liver metabolism of hydromorphone also means that it has fewer drug interactions than opioids that rely heavily on the cytochrome P450 system, though caution is still needed when combining it with other medications that affect the central nervous system 1.

From the FDA Drug Label

Hydromorphone is extensively metabolized via glucuronidation in the liver, with greater than 95% of the dose metabolized to hydromorphone-3-glucuronide along with minor amounts of 6-hydroxy reduction metabolites.

Yes, hydromorphone (Dilaudid) undergoes hepatic metabolism. The liver plays a significant role in metabolizing hydromorphone through glucuronidation, resulting in the production of hydromorphone-3-glucuronide and minor amounts of 6-hydroxy reduction metabolites 2.

From the Research

Hepatic Metabolism of Hydromorphone

• Hydromorphone is known to undergo hepatic metabolism, as stated in the study 3, where it is metabolized to analgesically inactive metabolites.
• The liver is the major site for biotransformation of most opioids, including hydromorphone, with the major metabolic pathway being oxidation 4.
• In patients with hepatic impairment, the disposition of hydromorphone is affected, with an important increase in bioavailability occurring after oral administration 5.
• The study 6 also mentions that hydromorphone has a high first-pass effect, which can lead to increased bioavailability and decreased clearance in patients with liver cirrhosis.
• Additionally, hydromorphone has been shown to depress hepatic glutathione concentrations in mice, which can influence the susceptibility of the liver to hepatotoxic agents 7.

Implications of Hepatic Metabolism

• The hepatic metabolism of hydromorphone can lead to the formation of inactive metabolites, which may accumulate in patients with renal insufficiency 4.
• The increased bioavailability and decreased clearance of hydromorphone in patients with hepatic impairment can result in increased concentrations and reduced plasma clearance of the drug, making it necessary to adjust the dose 5, 6.
• The study 3 highlights the need for further research on the pharmacokinetics and pharmacodynamics of hydromorphone, including its metabolism and potential toxicity in patients with liver disease.