CAJ | 학술논문

目的检测不同CYP3A5基因型的特发性膜性肾病患者应用他克莫司(TAC)后达到目标血药物浓度时的用药剂量,明确不同基因型与药物用量间的关系,初步探索TAC的最佳初始用药剂量.方法采用回顾性分析的方法,病例来自滨州医学院附属医院肾内科确诊的特发性膜性肾病患者60例,荧光染色原位杂交(FISH)法检测CYP3A5基因型.依据基因型将患者分为AA、AG 、GG 3组.均相酶扩大免疫分析法(EMIT)测定患者他克莫司的全血谷浓度(C0);比较3组患者用药后8、12、16、24周时他克莫司全血谷浓度(C0)、用药剂量、全血谷浓度与用药剂量(C0/D)的比值.按照临床疗效分为完全缓解(CR)、部分缓解(PR)和无效(NR)3组,比较各访视点患者的TAC药代动力学指标.结果 60例特发性膜性肾病患者CYP3A5基因多态性(A6986G)G的基因频率为53.33％,其中AA组12例(20％);AG组32例(53.33％);GG组16例(26.67％).3组患者他克莫司用药8、12、16、24周后的用药剂量、全血谷浓度/用药剂量比值的差异有统计学意义(均P＜ 0.05).AA组患者他克莫司用药剂量约为GG组的2～3倍,AG组约为GG组的1～2倍.治疗24周AA组患者的缓解率显著低于AG、GG组(16.67％比81.25％、16.67比87.25％,均P＜0.001).CR、PR组的C0以及C0/D值均较NR组高,且随用药时间延长而升高,但组间差异无统计学意义(P＞ 0.05).结论 CYP3A5基因多态性与他克莫司血药浓度明显相关,CYP3A5基因型检测对指导特发性膜性肾病患者的个体化用药有一定临床实用价值.
목적 검측불동CYP3A5기인형적특발성막성신병환자응용타극막사(TAC)후체도목표혈약물농도시적용약제량,명학불동기인형여약물용량간적관계,초보탐색TAC적최가초시용약제량.방법 채용회고성분석적방법,병례래자빈주의학원부속의원신내과학진적특발성막성신병환자60례,형광염색원위잡교(FISH)법검측CYP3A5기인형.의거기인형장환자분위AA、AG 、GG 3조.균상매확대면역분석법(EMIT)측정환자타극막사적전혈곡농도(C0);비교3조환자용약후8、12、16、24주시타극막사전혈곡농도(C0)、용약제량、전혈곡농도여용약제량(C0/D)적비치.안조림상료효분위완전완해(CR)、부분완해(PR)화무효(NR)3조,비교각방시점환자적TAC약대동역학지표.결과 60례특발성막성신병환자CYP3A5기인다태성(A6986G)G적기인빈솔위53.33％,기중AA조12례(20％);AG조32례(53.33％);GG조16례(26.67％).3조환자타극막사용약8、12、16、24주후적용약제량、전혈곡농도/용약제량비치적차이유통계학의의(균P＜ 0.05).AA조환자타극막사용약제량약위GG조적2～3배,AG조약위GG조적1～2배.치료24주AA조환자적완해솔현저저우AG、GG조(16.67％비81.25％、16.67비87.25％,균P＜0.001).CR、PR조적C0이급C0/D치균교NR조고,차수용약시간연장이승고,단조간차이무통계학의의(P＞ 0.05).결론 CYP3A5기인다태성여타극막사혈약농도명현상관,CYP3A5기인형검측대지도특발성막성신병환자적개체화용약유일정림상실용개치.
Objective To explore the effect of CYP3A5 gene polymorphisms on the whole blood trough concentration (C0) of tacrolimus (TAC) in patients with idiopathic membranous nephropathy to identify an economical and optimal initial dosage delivering the best curative effect with minimum drug adverse reaction.Methods Sixty patients with idiopathic membranous nephropathy were enrolled in this study.The CYP3A5 genotype was tested by fluorescence in situ hybridization (FISH).According to CYP3A5 genotype, the patients were divided into three groups (AA, AG, and GG).At the same time, the C0 of TAC was measured by enzyme multiplied immunoassay technique (EMIT).C0 of TAC, daily dosage of TAC and the concentration/dose(C0/D) ratio of TAC were detected after taking medicine at 8, 12, 16 and 24 weeks respectively, so as to corroborate the relation between CYP3A5 gene polymorphisms and the dosage of TAC.Results The oral TAC dosage had great variation among individuals.The occurrence of the CYP3A5 genetic polymorphisms (A6986G) designated as G was 53.33％.D and C0 were significantly different at 8, 12, 16 and 24 weeks respectively (all P ＜ 0.05).To reach the same C0, the patients with AA needed 2-3-fold dosage of TAC than GG;and those with AG needed 1-2-fold dosage of TAC than GG.After 24-week treatment, the effective rate of AA group was markedly lower than AG and GG (16.67％ vs 81.25％, 16.67％ vs 87.50％, all P ＜ 0.001).Among CR, PR and NR, there were no significantly difference on C0 or C0/D of TAC (P ＞ 0.05).Conclusions CYP3A5 genotypes are correlated with blood concentration of TAC.CYP3A5 genotyping may be a new approach to predict the optimal initial dosage of tacrolimus in idiopathic membranous nephropathy.