同时pharmacogenetics-based人口内药代动力学分析,例如在感染艾滋病毒的病人。

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甚J, Xinarianos G,米兰达C, Pushpakom年代,Cedeno年代,Clotet B,欧文,瓦莱米

同时pharmacogenetics-based人口内药代动力学分析,例如在感染艾滋病毒的病人。

Pharmacokinet。2013年7月,52(7):543 - 53年。doi: 10.1007 / s40262 - 013 - 0057 - 6。

PubMed ID

23494984 (在PubMed

]

文摘

背景:内是一个有效的HIV蛋白酶抑制剂。为了增强其药代动力学资料,内必须与例如流行性流感减毒活疫苗。有宽inter-patient可变性darunavir药物动力学中感染艾滋病毒的人,然而。内涌入运输车是一种已知的衬底,如1 a2和1 b1溶质载体有机阴离子转运蛋白家族成员(SLCO1A2 SLCO1B1),以及射流运输车等耐多药蛋白1 (MRP1)。目的:本研究的目的是开发一个semi-mechanistic人口内药代动力学模型,例如管理在感染艾滋病毒的成年人。所需的模型会将病人特点和遗传数据导致药物浓度和可变性也考虑两种化合物之间的相互作用。方法:人口与705年药代动力学分析血浆样本75高加索人接收darunavir /例如(600/100毫克每日两次)至少4周。至少有一个为每个参与者获得了完整的药动学特征,和内,例如在等离子体浓度测定高效液相色谱法。多用于148多态性基因编码转运蛋白、代谢酶是由两个方法:MALDI-TOF质谱分析和实时聚合酶链反应等位基因歧视。群体药代动力学模型为内开发,例如。 The effect of single nucleotide polymorphisms on the post hoc individual pharmacokinetic parameters was first explored using graphic methods and regression analysis. Those covariates related to changes in darunavir or ritonavir pharmacokinetic parameters were then further evaluated using non-linear mixed effects modeling (NONMEM version VII). RESULTS: Darunavir and ritonavir pharmacokinetics were best described by a two- and one-compartment model, respectively, both with first-order absorption and elimination. The darunavir peripheral volume of distribution decreased as alpha1-acid glycoprotein concentrations increased. Darunavir clearance was 12 % lower in patients with SLCO3A1 rs8027174 GT/TT genotypes, while homozygosity for the rs4294800 A allele was associated with 2.5-fold higher central volume of distribution. Body weight influenced ritonavir clearance. Ritonavir inhibited darunavir clearance following a maximum-effect model. CONCLUSION: A population pharmacokinetic model to simultaneously describe the pharmacokinetics of darunavir and ritonavir was developed in HIV-infected patients. The model provides better understanding of the interaction between darunavir and ritonavir and suggests an association between SLCO3A1 polymorphisms and darunavir pharmacokinetics. Bayesian estimates of individual darunavir parameters and ritonavir may be useful to predict darunavir exposure.

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药物转运蛋白

药物	转运体	类	生物	药理作用	行动
内	溶质载体有机阴离子转运蛋白家族成员1 b1	蛋白质	人类	未知的	抑制剂	细节