PDF(Pubmed)
Abstract：
The aim was to determine if opioid neuroimmunopharmacology pathway gene polymorphisms alter serum morphine, morphine-3-glucuronide and morphine-6-glucuronide concentration-response relationships in 506 cancer patients receiving controlled-release oral morphine. Morphine-3-glucuronide concentrations (standardised to 11 h post-dose) were higher in patients without pain control (median (interquartile range) 1.2 (0.7-2.3) versus 1.0 (0.5-1.9) μM, P = 0.006), whereas morphine concentrations were higher in patients with cognitive dysfunction (40 (20-81) versus 29 (14-60) nM, P = 0.02). TLR2 rs3804100 variant carriers had reduced odds (adjusted odds ratio (95% confidence interval) 0.42 (0.22-0.82), P = 0.01) of opioid adverse events. IL2 rs2069762 G/G (0.20 (0.06-0.52)), BDNF rs6265 A/A (0.15 (0.02-0.63)) and IL6R rs8192284 carrier (0.55 (0.34-0.90)) genotypes had decreased, and IL6 rs10499563 C/C increased (3.3 (1.2-9.3)), odds of sickness response (P ≤ 0.02). The study has limitations in heterogeneity in doses, sampling times and diagnoses but still suggests that pharmacokinetics and immune genetics co-contribute to morphine pain control and adverse effects in cancer patients.
摘要：
目的是确定阿片类神经免疫药理学通路基因多态性是否改变血清吗啡，506例接受控释口服吗啡的癌症患者中吗啡-3-葡糖苷酸和吗啡-6-葡糖苷酸的浓度-反应关系。吗啡-3-葡糖苷酸浓度（标准化至剂量后11小时）在没有疼痛控制的患者中更高（中位数（四分位距）1.2（0.7-2.3）对1.0（0.5-1.9）μM，P=0.006),而认知功能障碍患者的吗啡浓度较高（40（20-81）对29（14-60）nM，P=0.02)。TLR2rs3804100变异携带者的赔率降低（调整后的赔率比（95％置信区间）0.42（0.22-0.82），阿片类药物不良事件的P=0.01）。IL2rs2069762G/G(0.20(0.06-0.52)),BDNFrs6265A/A(0.15(0.02-0.63))和IL6Rrs8192284载体(0.55(0.34-0.90))基因型有所下降,IL6rs10499563C/C增加（3.3（1.2-9.3）），疾病反应的几率（P≤0.02）。该研究在剂量异质性方面有局限性，采样时间和诊断，但仍然表明，药代动力学和免疫遗传学共同有助于吗啡疼痛控制和癌症患者的不良反应。
