CYP2D6 genotype dependent oxycodone metabolism in postoperative patients.
CYP2D6 genotype dependent oxycodone metabolism in postoperative patients.
复制标题
DOI：
10.1371/journal.pone.0060239
复制
发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Musshoff F
中科院分区：
文献类型：
--
作者：
Stamer UM;Zhang L;Book M;Lehmann LE;Stuber F;Musshoff F
多态细胞色素P450 CYP2D6酶对羟考酮代谢及临床疗效的影响目前正在讨论中。然而，只有术后设置的备用数据。本研究的假设是基因型依赖性CYP2D6活性影响羟考酮及其代谢物的血浆浓度，并影响镇痛药的消耗。术后48小时，患者在麻醉结束前给予氧可酮0.05 mg/kg。在初始羟考酮剂量后30、90和180分钟抽取血样。采用电喷雾液相色谱-质谱联用技术分析氧可酮及其代谢物羟吗啡酮、去甲羟吗啡酮和去甲羟吗啡酮的血浆浓度。对121例患者进行CYP2D6基因分型，并将其分为以下基因型组：PM（代谢差者：无功能活性CYP2D6等位基因）、HZ/IM（杂合者，中间代谢者，CYP2D6活性降低）、EM（广泛代谢者，CYP2D6活性正常）和UM（超快速代谢者，CYP2D6活性升高）。主要终点为血浆氧吗啡酮/氧可酮浓度的基因型依赖性代谢物比值。次要终点是与标准非cyp依赖性阿片类药物吡曲胺相比，基因型依赖性镇痛药的消耗与等效镇痛剂量的计算。CYP2D6基因型之间的代谢存在差异。PM、HZ/IM、EM和UM的氧可酮/氧可酮平均比值（95% ci）分别为0.10（0.02/0.19）、0.13（0.11/0.16）、0.18（0.16/0.20）和0.28 (0.07/0.49)（p = 0.005）。截至12小时，PM的羟考酮消耗量最高（p = 0.005），导致PM的吡拉西米与羟考酮的等镇痛剂量最低(1.6 (1.4/1.8)；EM和um2.2 (2.1/2.3)；p < 0.001)。疼痛评分在基因型之间没有差异。在这种术后情况下，功能活跃的CYP2D6等位基因的数量对氧可酮代谢有影响。基因型也会影响镇痛药的消耗，从而导致吡曲胺和羟考酮等镇痛剂量的变化。在这个术后队列中，PCA技术满足了基因型不同的镇痛需求。
The impact of polymorphic cytochrome P450 CYP2D6 enzyme on oxycodone's metabolism and clinical efficacy is currently being discussed. However, there are only spare data from postoperative settings. The hypothesis of this study is that genotype dependent CYP2D6 activity influences plasma concentrations of oxycodone and its metabolites and impacts analgesic consumption. Patients received oxycodone 0.05 mg/kg before emerging from anesthesia and patient-controlled analgesia (PCA) for the subsequent 48 postoperative hours. Blood samples were drawn at 30, 90 and 180 minutes after the initial oxycodone dose. Plasma concentrations of oxycodone and its metabolites oxymorphone, noroxycodone and noroxymorphone were analyzed by liquid chromatography-mass spectrometry with electrospray ionization. CYP2D6 genotyping was performed and 121 patients were allocated to the following genotype groups: PM (poor metabolizer: no functionally active CYP2D6 allele), HZ/IM (heterozygous subjects, intermediate metabolizers with decreased CYP2D6 activity), EM (extensive metabolizers, normal CYP2D6 activity) and UM (ultrarapid metabolizers, increased CYP2D6 activity). Primary endpoint was the genotype dependent metabolite ratio of plasma concentrations oxymorphone/oxycodone. Secondary endpoint was the genotype dependent analgesic consumption with calculation of equianalgesic doses compared to the standard non-CYP dependent opioid piritramide. Metabolism differed between CYP2D6 genotypes. Mean (95%-CI) oxymophone/oxycodone ratios were 0.10 (0.02/0.19), 0.13 (0.11/0.16), 0.18 (0.16/0.20) and 0.28 (0.07/0.49) in PM, HZ/IM, EM and UM, respectively (p = 0.005). Oxycodone consumption up to the 12th hour was highest in PM (p = 0.005), resulting in lowest equianalgesic doses of piritramide versus oxycodone for PM (1.6 (1.4/1.8); EM and UM 2.2 (2.1/2.3); p<0.001). Pain scores did not differ between genotypes. In this postoperative setting, the number of functionally active CYP2D6 alleles had an impact on oxycodone metabolism. The genotype also impacted analgesic consumption, thereby causing variation of equianalgesic doses piritramide : oxycodone. Different analgesic needs by genotypes were met by PCA technology in this postoperative cohort.
登录
查看更多内容
影响因子：
6.7
作者：
通讯作者：
--
影响因子：
3.2
作者：
Gronlund, Juha;Saari, Teijo I.;Olkkola, Klaus T.
通讯作者：
Olkkola, Klaus T.
影响因子：
4.7
作者：
Maddocks, I;Somogyi, A;Parker, D
通讯作者：
Parker, D
影响因子：
2.3
作者：
Musshoff, F.;Trafkowski, J.;Madea, B.
通讯作者：
Madea, B.
影响因子：
2.9
作者：
Naito, Takafumi;Takashina, Yoshiaki;Kawakami, Junichi
通讯作者：
Kawakami, Junichi