Kotb Hassan Ibraheem Mohamed, Fouad Ihab Ahmed, Fares Khaled Mohamed, Mostafa Mostafa Galal, Abd El-Rahman Ahmad M
Assiut University Hospital, Anesthesia, Intensive Care, and Pain Management, Assiut, Egypt.
J Opioid Manag. 2008 Mar-Apr;4(2):99-104. doi: 10.5055/jom.2008.0014.
There are no studies reported on pharmacokinetics of opioids in patients with hepatocellular carcinoma, the fifth most common cancer in the world.
The authors have studied the pharmacokinetic profile of oral tramadol (50 mg) capsule in 20 patients with liver carcinoma (10 with primary carcinoma on top of chronic hepatitis C and 10 with secondary metastatic liver malignancy as a result of other primary) compared with 10 healthy controls. Plasma tramadol concentrations were measured in venous samples at intervals up to 12 hours by high-pressure liquid chromatography. Allpharmacokinetic variables were evaluated using one-compartment model.
Tramadol bioavailability showed a substantial increase in patients with primary liver cancer and secondary metastatic than that of control (98 percent, 75 percent, and 68 percent, respectively). The area under the serum concentration-time curve increased significantly in patients with primary and metastatic cancer of liver than in control [1,933 microg/h/L (SD = 41), 1,327 microg/h/L (SD = 51), 1,138.5 microg/h/L (SD = 31), respectively]. Also, a significant difference in Cmax and Tmax was found between patients with malignant liver and control. Reduced clearance and impaired elimination was significantly observed in patients with liver carcinoma than control. Clearance was reduced to 50 percent of control, and elimination halflife increased up to three folds in patients with primary liver carcinoma than that of control. Satisfactory pain relief with minimal side effects was observed all over study period.
It is recommended to lengthen the dose interval of oral tramadol, if it is to be used in patients with liver cancer for analgesic purposes, to 50 mg every 12 hours as it is proved to be effective and safe.
肝细胞癌是世界上第五大常见癌症，目前尚无关于阿片类药物在肝细胞癌患者体内药代动力学的研究报道。
作者研究了20例肝癌患者（10例为慢性丙型肝炎基础上的原发性肝癌，10例为其他原发性癌症导致的继发性肝转移恶性肿瘤）口服曲马多（50毫克）胶囊的药代动力学特征，并与10名健康对照者进行比较。通过高压液相色谱法，每隔一定时间测量静脉血样中的曲马多血浆浓度。所有药代动力学变量均采用单室模型进行评估。
与对照组相比，原发性肝癌和继发性转移癌患者的曲马多生物利用度显著增加（分别为98%、75%和68%）。肝癌原发性和转移性患者血清浓度-时间曲线下面积比对照组显著增加[分别为1933微克/小时/升（标准差=41）、1327微克/小时/升（标准差=51）、1138.5微克/小时/升（标准差=31）]。此外，肝恶性肿瘤患者与对照组之间的Cmax和Tmax存在显著差异。与对照组相比，肝癌患者的清除率降低且消除受损明显。原发性肝癌患者的清除率降至对照组的50%，消除半衰期比对照组增加了两倍。在整个研究期间，观察到疼痛缓解满意且副作用最小。
如果将口服曲马多用于肝癌患者镇痛，建议将给药间隔延长至每12小时50毫克，因为已证明其有效且安全。
