Critical Care Medicine-Renal, Electrolyte and Acid Base Disorders>>>>>Drug Dosing in Renal Failure
Question 6#

A 70-year-old male with mild dementia and history of intravenous drug abuse, currently on methadone, was admitted to the ICU with obstructive nephropathy. Based on the initial workup, it is likely secondary to advanced prostate cancer with metastatic disease to the bones. He has postobstructive renal acute kidney injury and has been admitted for further care. He was placed on his home dose of methadone.

Which of the following is TRUE regarding methadone?

A. Methadone undergoes extensive hepatic metabolism by the cytochrome P450 family
B. Methadone has two main active metabolites
C. The primary elimination of methadone is through the liver
D. In addition to its action on the mu receptors, methadone also acts as an agonist to n-methyl-d-aspartate (NMDA) receptors

Correct Answer is A

Comment:

Correct Answer: A

Methadone is a unique opioid medication with a long duration of action that can be useful in the treatment of opioid addiction. It is also used for cancer-related pain and chronic pain conditions. Methadone is a mureceptor agonist and an NMDA receptor antagonist. Similar to other opioids, it undergoes hepatic metabolism by the cytochrome P450 family via N-methylation. It has no active metabolites. Fecal elimination is the primary process through which methadone is excreted. There is a minimal amount of renal elimination. Therefore, there is no need for a dose adjustment for those with renal dysfunction.

References:

1. https://pdfs.semanticscholar.org/17b3/8e679ae89e851b66dc301d85b443255e52.
2. https://www.drugbank.ca/drugs/DB00333.
3. Kharasch ED, Regina KJ, Blood J, Friedel C. Methadone pharmacogenetics CYP2B6 polymorphisms determine plasma concentrations, clearance, and metabolism. Anesthesiology. 2015;123(5):1142-1153.