Clinical Pharmacokinetics of Methadone

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.

Usefulness of high capacity acetaminophen suppository in cancer pain patients

<b>Purpose</b>: In Japan, the daily dosage limit of acetaminophen is considered to be 1500mg: however, in Europe and the USA, the daily dosage limit of acetaminophen for patients with cancer pain is 4000 mg. In Japan, only 100 mg and 200 mg acetaminophen suppositories are available, which means that cancer pain patients may need to insert up to 3 - 4 acetaminophen suppositories at the same time. Therefore, in this study, we examined the efficacy of 600 and 800 mg suppositories prepared at our hospital. <b>Methods</b>: We measured the serum concentrations of acetaminophen in cancer pain patients prescribed either oral or the rectal formulation of acetaminophen, and examined the side effects of the drug. <b>Results</b>: Our results revealed similar mean blood concentrations of acetaminophen in both the oral and rectal group of patients, and the serum AST, ALT and total bilirubin levels were within normal range in all the cancer pain patients prescribed acetaminophen. <b>Conclusion</b>: Our results suggest good bioavailability of acetaminophen from the acetaminophen suppositories in our cancer pain patients.