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.

OBJECTIVE: Rikkunshito, an herbal medicine, is widely prescribed in Japan for the treatment of anorexia and functional dyspepsia, and has been reported to recover reductions in food intake caused by cisplatin. We investigated whether rikkunshito could improve chemotherapy-induced nausea and vomiting (CINV) and anorexia in patients treated with cisplatin. METHODS: Patients with uterine cervical or corpus cancer who were to receive cisplatin (50 mg/m² day 1) and paclitaxel (135 mg/m² day 0) as first-line chemotherapy were randomly assigned to the rikkunshito group receiving oral administration on days 0–13 with standard antiemetics, or the control group receiving antiemetics only. The primary endpoint was the rate of complete control (CC: no emesis, no rescue medication, and no significant nausea) in the overall phase (0–120 hours). Two-tailed p<0.20 was considered significant in the planned analysis. RESULTS: The CC rate in the overall phase was significantly higher in the rikkunshito group than in the control group (57.9% vs. 35.3%, p=0.175), as were the secondary endpoints: the CC rate in the delayed phase (24–120 hours), and the complete response (CR) rates (no emesis and no rescue medication) in the overall and delayed phases (63.2% vs. 35.3%, p=0.095; 84.2% vs. 52.9%, p=0.042; 84.2% vs. 52.9%, p=0.042, respectively), and time to treatment failure (p=0.059). Appetite assessed by visual analogue scale (VAS) appeared to be superior in the rikkunshito group from day 2 through day 6. CONCLUSION: Rikkunshito provided additive effect for the prevention of CINV and anorexia.
Administration, Oral ; Anorexia* ; Antiemetics ; Appetite ; Cisplatin* ; Drug Therapy ; Dyspepsia ; Eating ; Herbal Medicine* ; Humans ; Japan ; Nausea* ; Paclitaxel* ; Time-to-Treatment ; Vomiting*

Purpose: The purpose of this study is to evaluate hangeshashinto rinse for oral discomfort in terminally-ill cancer patients and to compare the effectiveness of hangeshashinto rinse with or without honey rinse. Methods: Patients with oral discomfort were randomized to receive either hangeshashinto rinse or hangeshashinto with honey rinse as first-line treatment. Patients performed oral rinse three to five times a day for 2 weeks. Further, oral wetness, halitosis, oral mucositis, mouth discomfort, compliance of rinse were then evaluated before and after the intervention. Results: 144 patients were enrolled during this period and 22 patients completed the study (hangeshashinto 13 / hangeshashinto with honey 9). After the intervention, oral wetness was improved, and end-tidal concentration of hydrogen sulfide was decreased in both cases. Although there was no statistically significant difference, oral discomfort by subjective and objective evaluations, also and symptom of oral mucositis were improved. Other volatile sulfur compounds decreased. Frequency of rinsing between groups receiving hangeshashinto or hangeshashinto with honey did not differ, however, the acceptability was slightly better in the honey combination group. Conclusion: Both hangeshashinto rinse and hangeshashinto with honey rinse reduced end-tidal concentration of hydrogen sulfide and improved oral wetness. Oral rinse by hangeshashinto or hangeshashinto with honey may be effective for oral discomfort in terminally-ill cancer patients.