Methadone oral tablets initially became available on the Japanese market in MAR－2013. Methadone, which has different pharmacological properties from other opioids including morphine, can cause serious adverse drug reactions such as respiratory depression and QT prolongation. One of the causes of these reactions is its extremely complex pharmacokinetics. Methadone is mostly metabolized in the liver, with a variety of metabolic enzymes, including cytochrome P450 (CYP) 3A4, CYP2B6, and CYP2D6, being involved. The characteristics of methadone include self-induction of metabolism, delayed excretion due to alkaline urine, and an extremely long half-life requiring a long time to achieve a steady state. Without a full understanding of its complex pharmacokinetics, the blood concentration of methadone is not maintained at a constant level, and serious adverse events could happen due to an unexpected increase in its blood concentration. Herein, for safe clinical use by physicians and pharmacists, we summarize the pharmacokinetics of methadone.

A 47-year-old male complaining of dyspnea and fever was admitted to our hospital and regurgitation of the aortic and mitral valves with mitral valve aneurysm due to infective endcarditis was diagnosed. The non-coronary and the right coronary cusps of the aortic valve had amount of vegetations, and also the anterior leaflet of the mitral valve had an aneurysm with vegetations. Both aortic and mitral valve replacement were performed. The postoperative clinical course was uneventful.

Primary malignant cardiac tumors are extremely rare. Among these, leiomyosarcoma are particularly exceptional and only about 20 surgically treated cases have been extensively described. We describe a case of right atrial leiomyosarcoma which was accidentally found by computed tomography. The tumor was surgically resected under extracorporeal circulation. Two months later the patient had cerebral hemorrhage due to a brain metastasis, which almost completely disappeared after irradiation. There was no other evidence of recurrence for 12 months after operation.