Pharmacokinetics of opioids in liver disease

Citation
I. Tegeder et al., Pharmacokinetics of opioids in liver disease, CLIN PHARMA, 37(1), 1999, pp. 17-40
Citations number
255
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Pharmacology,"Pharmacology & Toxicology
Journal title
CLINICAL PHARMACOKINETICS
ISSN journal
0312-5963 → ACNP
Volume
37
Issue
1
Year of publication
1999
Pages
17 - 40
Database
ISI
SICI code
0312-5963(199907)37:1<17:POOILD>2.0.ZU;2-E
Abstract
The liver is the major site of biotransformation for most opioids. Thus, th e disposition of these drugs may be affected in patients with liver insuffi ciency. The major metabolic pathway for most opioids is oxidation. The exce ptions are morphine and buprenorphine, which primarily undergo glucuronidat ion, and remifentanil, which is cleared by ester hydrolysis. Oxidation of opioids is reduced in patients with hepatic cirrhosis, resulti ng in decreased drug clearance [for pethidine (meperidine), dextroprogoxyph ene, pentazocine, tramadol and alfentanil] and/or increased oral bioavailab ility caused by a reduced first-pass metabolism (for pethidine, dextropropo xyphene, pentazocine and dihydrocodeine). Although glucuronidation is thoug ht to be less affected in liver cirrhosis, the clearance of morphine was fo und to be decreased and oral bioavailability increased. The consequence of reduced drug metabolism is the risk of accumulation in t he body, especially with repeated administration. Lower doses or longer adm inistration intervals should be used to remedy this risk. Special risks are known for pethidine, with the potential for the accumulation of norpethidi ne, a metabolite that can cause seizures, and for dextropropoxyphene, for w hich several cases of hepatotoxicity have been reported. On the other hand, the analgesic activity of codeine and tilidine depends on transformation i nto the active metabolites, morphine and nortilidine, respectively. If meta bolism is decreased in patients with chronic liver disease, the analgesic a ction of these drugs may be compromised, Finally, the disposition of a few opioids, such as fentanyl, sufentanil and remifentanil, appears to be unaff ected in liver disease.