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.

[Effect of magnesium supplementation on early-stage hypomagnesemia in patients treated with cetuximab].

Cetuximab is a monoclonal antibody that binds to the EGFR, and is used in patients with colorectal cancer. The most common toxicities associated with the use of cetuximab are rash and hypomagnesemia. Hypomagnesemia is a major adverse event, but it has often been ignored in past studies and its management has not been characterized. The aim of this study was to obtain a better understanding of the overall incidence of hypomagnesemia and to evaluate the usefulness of our original treatment guidelines for hypomagnesemia in patients receiving cetuximab-based therapy. We investigated 15 patients who were treated with cetuximab(with or without combined chemotherapy)between October 2008 and November 2010. Thirteen patients developed hypomagnesemia: 11 patients had Grade 1, one patient had Grade 2, and one patient had severe hypomagnesemia(Grade 3). Grade 1 hypomagnesemia was observed after an average of 7. 5±4. 8 weeks of treatment. None of the patients developed Grade 2 or higher hypomagnesemia after the implementation of our treatment guidelines. In conclusion, cetuximab treatment is associated with a significant risk of hypomagnesemia. The early monitoring and effective management of hypomagnesemia are important for patients receiving cetuximab-based therapy.

[Pharmacokinetic study of amrubicin in a case of small lung cancer on hemodialysis].

Amrubicin is a new anticancer drug that has been shown to exert efficacy against small cell lung cancer. The pharmacokinetic parameters of amrubicin have not yet been investigated in hemodialysis patients, although it had been expected that amrubicin might not be cleared by hemodialysis because of its high lipid solubility, high protein binding rate and low urinary excretion rate. We encountered a case of small cell lung cancer on hemodialysis who was treated with amrubicin. We assayed the plasma concentrations of amrubicin and amrubicinol (its active metabolite) and analyzed the pharmacokinetic parameters of the drug in this hemodialysis patient. The results revealed that the pharmacokinetic parameters of the drug in this patient undergoing hemodialysis were similar to those in patients not on hemodialysis. Our results suggest that amrubicin and amrubicinol are cleared by hemodialysis, and that dose adjustment of amrubicin might not be required in hemodialysis patients.

[Effect of withdrawal of 5-fluorouracil bolus administration on recovery from neutropenia in colorectal cancer patients treated with mFOLFOX6 chemotherapy-comparison with total dosage reduction].

A combination of oxaliplatin(L-OHP), folinic acid and 5-fluorouracil(5-FU)(mFOLFOX6)has been widely administered to treat advanced or recurrent colorectal cancer. In this regimen, a bolus of 5-FU is administered intravenously, followed by its 46-hr continuous intravenous infusion. For 12 patients who showed neutropenia during mFOLFOX6 chemotherapy at Itami City Hospital, we investigated neutrophil recovery by comparing a patient group treated by the withdrawal of the 5-FU bolus administration(n=6)with a patient group treated by total dose reduction of L-OHP, as well as both the bolus and continuous 5-FU administration(n=6). After two weeks, the neutrophil numbers in the bolus withdrawal group showed a relatively higher value than that in the total dose reduction group[p= 0.032]. For patients showing neutropenia related to mFOLFOX6 chemotherapy, withdrawal of 5-FU bolus administration is suggested to be an effective method of promoting the recovery of neutrophil numbers.