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首页> 外文期刊>The Journal of Clinical Pharmacology: Official Journal of the American College of Clinical Pharmacology >Sequential Analysis of Tacrolimus Dosing in Adult Lung Transplant Patients With ABCB1 Haplotypes.
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Sequential Analysis of Tacrolimus Dosing in Adult Lung Transplant Patients With ABCB1 Haplotypes.

机译：成人ABCB1单倍型肺移植患者他克莫司剂量的顺序分析。

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摘要

The genetic polymorphisms in the ABCB1 gene, which encodes for the membrane pump, P-glycoprotein, have been previously demonstrated to have an association with tacrolimus dosing in organ transplant patients. This study associated the haplotype and genotype for ABCB1 G2677T and C3435T variants with a sequential analysis of tacrolimus blood level (ng/mL) per mg/day dosage ([L/D]) administered to 91 adult lung transplant patients at 1, 3, 6, 9, and 12 months after transplantation. Haplotype 22 carriers had a significantly higher tacrolimus [L/D] value in comparison with nonhaplotype 22 carriers (P = .04) only at 1 month after transplant. Sequential analysis demonstrated that ABCB1 genotypes 00 and 01 had low tacrolimus [L/D] values at 1 and 3 months, but these values increased substantially at 6, 9, and 12 months after transplantation. This was not true of the other genotypes with the exception of genotypes 10 and 21, which had small numbers of patients but had consistently low tacrolimus [L/D]. Haplotypeanalysis also suggested that the homozygous for ABCB1 2677 variant allele had more of an impact on tacrolimus [L/D] in haplotype analysis than that of ABCB1 3435. In conclusion, sequential analysis of tacrolimus [L/D] with haplotypes can explain previous clinical observations of changes in tacrolimus dosage over time but suggests that this effect is limited to individual patient haplotypes. Sequential analysis of drug dosing and haplotypes relationships can provide important information about the induction or inhibition of drug-drug and disease-drug interactions among specific haplotypes.
机译：先前已证明，ABCB1基因的遗传多态性编码膜泵P-糖蛋白，与他克莫司的剂量与器官移植患者的剂量有关。这项研究将ABCB1 G2677T和C3435T变体的单倍型和基因型与他克莫司血水平（ng / mL）/ mg /日剂量（[L / D]）的顺序分析相联系，该剂量分别以1,3，移植后6、9和12个月。仅在移植后1个月，单倍型22携带者的他克莫司[L / D]值显着高于非单倍型22携带者（P = .04）。顺序分析表明，ABCB1基因型00和01在1和3个月时他克莫司[L / D]值低，但这些值在移植后6、9和12个月时显着增加。除基因型10和21外，其他基因型的患者数量很少，但他克莫司的持续性较低[L / D]，而其他基因型则并非如此。单倍型分析还表明，与单倍型ABCB1 3435相比，ABCB1 2677变异等位基因的纯合子对他克莫司[L / D]的影响更大。他克莫司剂量随时间变化的观察结果，但表明这种作用仅限于单个患者单倍型。药物剂量和单倍型关系的顺序分析可以提供有关特定单倍型之间药物或药物相互作用以及疾病-药物相互作用的重要信息。

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