Population Pharmacokinetics of Methadone after Oral Administration in Japanese Patients with Cancer-Related Pain.

Methadone tablets were approved for use in Japan in March 2013. The metabolism of methadone is complex and executed mainly by the cytochromes, CYP3A4 and CYP2B6. The aim of this study was to evaluate the pharmacokinetics of methadone upon oral administration in Japanese patients who experienced cancer-related pain. The concentration of the drug in blood samples was measured in 25 patients undergoing methadone therapy, and the factors leading to variations were investigated. A population pharmacokinetic analysis was evaluated using the Phoenix® NLMETM software. Based on this, the ALBI (albumin-bilirubin) score was identified as a significant factor that could be used to assess variations in the serum concentration of methadone, which was then incorporated into the following final model formula: clearance (L/h) = 5.38 × (ALBI score/-2.139)1.88. The results of these pharmacokinetic parameters suggested that, in clinical use, the dose of methadone should be reduced if liver function declined in patients with cancer-related pain.