Kokubun Hideya, Takigawa Chizuko, Miyano Kanako, Uezono Yasuhito
Tokyo University of Pharmacy and Life Sciences.
Department of Palliative Medicine, KKR Sapporo Medical Center.
Biol Pharm Bull. 2018;41(4):649-651. doi: 10.1248/bpb.b17-00691.
In March 2013, the clinical use of oral methadone tablets was initiated in Japan. There are many factors responsible for the change in blood concentrations of methadone, and its pharmacokinetics is very complex. Therefore, a simple and accurate measurement method for methadone blood concentrations was developed using HPLC/electrochemical detector (ECD). An eluent of 10 mM NaHPO/CHCN/CHOH (20 : 19 : 3) was used as the mobile phase. The column was used the XTerra RP18, and the voltage of the ECD was set at 400 to 800 mV. As a result, the calibration curve was linear in the ranges of 10 to 100 ng/mL (y=5012.7x+1041.1, r=0.999). The intra- and inter-day coefficients of variation were <5.2 and <5.8%, respectively. Therefore, this method was considered to be useful for the measurement of methadone blood levels in cancer patients. Also, using this method, blood methadone concentration was measured over time in a patient with cancer-associated pain who was treated with methadone. The estimated clearance (CL/F) and distribution volume (V/F) of methadone were 2.84 L/h and 502.8 L, respectively, and took about two weeks to reach steady state.
2013年3月，日本开始临床使用口服美沙酮片。美沙酮血药浓度变化的影响因素众多，其药代动力学非常复杂。因此，采用高效液相色谱/电化学检测器（ECD）建立了一种简单准确的美沙酮血药浓度测定方法。以10 mM NaHPO/乙腈/甲醇（20∶19∶3）作为流动相洗脱液。色谱柱采用XTerra RP18，ECD的电压设置为400至800 mV。结果，校准曲线在10至100 ng/mL范围内呈线性（y = 5012.7x + 1041.1，r = 0.999）。日内和日间变异系数分别<5.2%和<5.8%。因此，该方法被认为可用于测定癌症患者的美沙酮血药浓度。此外，使用该方法，对一名接受美沙酮治疗的癌症相关疼痛患者的美沙酮血药浓度进行了长期监测。美沙酮的估计清除率（CL/F）和分布容积（V/F）分别为2.84 L/h和502.8 L，达到稳态约需两周时间。
