本文選題：CYP3A5　切入點(diǎn)：CYP3A4　出處：《山西醫(yī)科大學(xué)》2015年碩士論文　論文類型：學(xué)位論文

【摘要】：目的:了解CYP3A4和CYPA5對FK506代謝與清除的影響,比較傳統(tǒng)給藥和根據(jù)基因分型進(jìn)行個(gè)體化給藥的優(yōu)劣,了解CYP3A4和CYPA5聯(lián)合基因分型的臨床應(yīng)用價(jià)值。方法:選取2014年5月至12月在解放軍第309醫(yī)院隨診的75例腎移植受者為研究對象,隨機(jī)入組(實(shí)驗(yàn)組和對照組),所有納入實(shí)驗(yàn)組的腎移植受者于術(shù)前采用熒光原位雜交法測定腎移植受體CYP3A5、CYP3A4的基因型,實(shí)驗(yàn)組根據(jù)CYP3A5-CYP3A4基因型進(jìn)行分組并給予不同的FK506初始劑量。對照組三個(gè)月后進(jìn)行回顧性基因分型。結(jié)果:①我研究所腎移植受者CYP3A5*3和CYP3A4*18B等位基因突變頻率分別為67.3%和20%,與國內(nèi)外研究數(shù)據(jù)結(jié)果相似,說明中國人種CYP3A5*3和CYP3A4*18B基因分布穩(wěn)定。②腎移植受者CYP3A5*3和CYP3A4*18B基因多態(tài)性影響FK506的藥代動(dòng)學(xué)。CYP3A5*1和CYP3A4*18B促進(jìn)代謝,CYP3A5*3和CYP3A4*1延緩代謝。③腎移植術(shù)后早期根據(jù)基因型調(diào)整給予個(gè)體化精細(xì)他克莫司治療可以使腎移植受者更快地達(dá)到標(biāo)準(zhǔn)血藥濃度范圍。④術(shù)后早期聯(lián)合高表達(dá)的腎移植受者為達(dá)到目標(biāo)血藥濃度范圍所需藥物劑量較高,個(gè)體化給藥能夠使移植受者迅速有效達(dá)到目標(biāo)血藥濃度,而傳統(tǒng)給藥劑量往往無法達(dá)標(biāo),誘發(fā)排斥反應(yīng)的風(fēng)險(xiǎn)較高,有統(tǒng)計(jì)學(xué)顯著差異。結(jié)論:與傳統(tǒng)方法相比,根據(jù)基因型的不同調(diào)整FK506的初始劑量的個(gè)體化給藥方案可以明顯提高腎移植術(shù)后早期FK506藥物血藥濃度和達(dá)到標(biāo)準(zhǔn)血藥濃度范圍的百分比,為降低因藥物濃度過高或者過低引起的藥物不良反應(yīng)、急性排斥反應(yīng)的發(fā)生提供了可能。
[Abstract]:Objective: to investigate the effects of CYP3A4 and CYPA5 on the metabolism and clearance of FK506 and compare the advantages and disadvantages of traditional administration and individualized administration according to genotyping. To understand the clinical application value of CYP3A4 and CYPA5 combined genotyping. Methods: 75 renal transplant recipients who were followed up from May 2014 to December in the 309th Hospital of PLA were selected as the study subjects. The genotypes of CYP3A5 and CYP3A4 were determined by fluorescence in situ hybridization (FISH) in all the renal transplant recipients of the experimental group and the control group, and the genotypes of CYP3A5 and CYP3A4 were determined by fluorescence in situ hybridization. The experimental group was divided into groups according to CYP3A5-CYP3A4 genotype and given different initial doses of FK506. The control group was genotyped retrospectively after three months. Results the frequencies of CYP3A5*3 and CYP3A4*18B alleles were 67.3% and 67.3% respectively in the recipients of kidney transplantation in the study group. 20, similar to domestic and foreign research data, The results indicate that the polymorphism of CYP3A5*3 and CYP3A4*18B genes in Chinese ethnic CYP3A5*3 and CYP3A4*18B gene distribution is stable. 2. The pharmacokinetics of FK506. CYP3A5A5O1 and CYP3A4*18B promote metabolism. CYP3A5A5K3 and CYP3A4*1 delay metabolism 3 early after renal transplantation according to genotypic adjustment. Chemotherapy with tacrolimus could enable renal transplant recipients to reach the standard plasma drug concentration range faster. 4. 4 early postoperative high expression renal transplant recipients needed higher doses of drugs to reach the target blood drug concentration range. Individualized administration can quickly and effectively reach the target blood drug concentration in the transplant recipients, but the traditional dose often fails to meet the standard, and the risk of inducing rejection is higher. Conclusion: compared with the traditional method, the risk of inducing rejection is significantly higher. The individualized regimen of adjusting the initial dose of FK506 according to different genotypes could significantly increase the blood concentration of FK506 and the percentage of reaching the standard range of serum drug concentration in the early stage of renal transplantation. In order to reduce the adverse drug reaction caused by too high or too low drug concentration, the occurrence of acute rejection is possible.
【學(xué)位授予單位】：山西醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R699.2

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本文編號：1619006