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.

Background: Choosing catecholamines, such as norepinephrine and dopamine, for perioperative blood pressure control is essential for anesthesiologists and intensivists. However, studies specific to noncardiac surgery are limited. Therefore, we aimed to evaluate the effects of postoperative norepinephrine and dopamine on clinical outcomes in adult noncardiac surgery patients by analyzing a nationwide intensive care patient database. Methods: The Japanese Intensive care PAtient Database (JIPAD) was used for this multicenter retrospective study. Adult patients in the JIPAD who received norepinephrine or dopamine within 24 h after noncardiac surgery in 2018–2020 were included. We compared the norepinephrine and dopamine groups using a one-to-one propensity score matching analysis. The primary outcome was in-hospital mortality. Secondary outcomes were intensive care unit (ICU) mortality, hospital length of stay, and ICU length of stay. Results: A total of 6,236 eligible patients from 69 ICUs were allocated to the norepinephrine (n = 4,652) or dopamine (n = 1,584) group. Propensity score matching was used to create a matched cohort of 1,230 pairs. No differences in the in-hospital mortality was found between the two propensity score matched groups (risk difference: 0.41%, 95% CI [−1.15, 1.96], P = 0.608). Among the secondary outcomes, only the ICU length of stay was significantly shorter in the norepinephrine group than in the dopamine group (median length: 3 vs. 4 days, respectively; P < 0.001). Conclusions In adult patients after noncardiac surgery, norepinephrine was not associated with decreased mortality but was associated with a shorter ICU length of stay than dopamine.

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.