Kotb H I M, El-Kady S A, Emara S E S, Fouad E A, El-Kabsh M Y
Department of Anesthesia, Faculty of Medicine, Assiut University, Assiut, Egypt.
Br J Anaesth. 2005 Jan;94(1):95-9. doi: 10.1093/bja/aei007. Epub 2004 Oct 29.
There are no studies reported on the pharmacokinetics of controlled release morphine (MST) in patients with hepatocellular carcinoma, the fifth most common cancer in the world.
We have studied the pharmacokinetic profile of MST (30 mg) in 15 patients with liver carcinoma (eight with primary carcinoma on top of chronic hepatitis C, and seven with secondary metastatic liver malignancy as a result of other primary) compared with our previously published data for 10 healthy controls. Plasma morphine concentrations were measured in venous blood samples at intervals up to 12 h by high-pressure liquid chromatography. Total body clearance (Cl) and systemic bioavailability were estimated using a compartmental method.
Morphine bioavailability showed a substantial increase in patients with primary liver and secondary metastatic carcinoma than that of controls (64.8, 62.1, and 16.8%, respectively). The area under the serum concentration-time curve increased 4-fold in primary carcinoma (416 [sem25] microg h(-1) litre(-1)) and 3-fold (303 [21] microg h(-1) litre(-1)) in metastatic liver patients compared with healthy control (92.5 [3] microg h(-1) litre(-1)). No significant difference was found in T(max) between the two malignant groups but C(max) was significantly greater in primary liver carcinoma patients. Impaired morphine elimination was noted in primary carcinoma only (t(1/2) 5.99 [0.39] h).
Careful administration of morphine is recommended in patients with liver cancer.
世界上第五大常见癌症——肝细胞癌患者中，关于控释吗啡（美施康定，MST）药代动力学的研究尚无报道。
我们研究了15例肝癌患者（8例慢性丙型肝炎基础上的原发性肝癌患者，7例其他原发性肿瘤导致的继发性肝转移恶性肿瘤患者）服用MST（30毫克）后的药代动力学情况，并与我们之前发表的10例健康对照者的数据进行比较。通过高压液相色谱法，每隔一定时间测量静脉血样本中的血浆吗啡浓度。采用房室模型法估算总体清除率（Cl）和全身生物利用度。
与对照组相比，原发性肝癌和继发性肝癌患者的吗啡生物利用度显著增加（分别为64.8%、62.1%和16.8%）。与健康对照者（92.5 [3] 微克·小时⁻¹·升⁻¹）相比，原发性肝癌患者血清浓度-时间曲线下面积增加了4倍（416 [标准误25] 微克·小时⁻¹·升⁻¹），转移性肝癌患者增加了3倍（303 [21] 微克·小时⁻¹·升⁻¹）。两组恶性肿瘤患者的达峰时间（T(max)）无显著差异，但原发性肝癌患者的峰浓度（C(max)）显著更高。仅在原发性肝癌患者中发现吗啡清除受损（半衰期（t(1/2)）为5.99 [0.39] 小时）。
建议肝癌患者谨慎使用吗啡。
