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https://www.readbyqxmd.com/read/28718515/impact-of-single-nucleotide-polymorphisms-on-plasma-concentrations-of-efavirenz-and-lopinavir-ritonavir-in-chinese-children-infected-with-the-human-immunodeficiency-virus
#1
Xia Liu, Qing Ma, Yan Zhao, Weiwei Mu, Xin Sun, Yuewu Cheng, Huiping Zhang, Ye Ma, Fujie Zhang
Single-nucleotide polymorphisms (SNPs) in the genes that encode the cytochrome P450 (CYP) drug metabolizing enzymes and drug transporters have been reported to influence antiretroviral drug pharmacokinetics. While primarily metabolized by CYP2B6 and -3A, efavirenz (EFV) and lopinavir/ritonavir (LPV/r) are substrates of P-glycoprotein and solute carrier organic (SLCO) anion transporter, respectively OBJECTIVE: To investigate the association between SNPs and efavirenz (EFV) or lopinavir/ritonavir (LPV/r) concentrations in Chinese children infected with the human immunodeficiency virus (HIV) METHODS: Genotyping was performed on CYP2B6 516G→T, -1459C→T, and -983T→C, ABCB1 3435C→T, and SLCO1B1 521T→C in 229 HIV-infected Chinese pediatric patients with an age range from 4...
July 17, 2017: Pharmacotherapy
https://www.readbyqxmd.com/read/28653144/explaining-ethnic-variability-of-transporter-substrate-pharmacokinetics-in-healthy-asian-and-caucasian-subjects-with-allele-frequencies-of-oatp1b1-and-bcrp-a-mechanistic-modeling-analysis
#2
Rui Li, Hugh A Barton
BACKGROUND: Ethnic variability in the pharmacokinetics of organic anion transporting polypeptide (OATP) 1B1 substrates has been observed, but its basis is unclear. A previous study hypothesizes that, without applying an intrinsic ethnic variability in transporter activity, allele frequencies of transporters cannot explain observed ethnic variability in pharmacokinetics. However, this hypothesis contradicts the data collected from compounds that are OATP1B1 substrates but not breast cancer resistance protein (BCRP) substrates...
June 26, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28627804/the-effect-of-genetic-polymorphisms-in-slco2b1-on-the-lipid-lowering-efficacy-of-rosuvastatin-in-healthy-adults-with-elevated-low-density-lipoprotein
#3
Tae-Eun Kim, Dong-Seong Shin, Namyi Gu, Byung Hwa Jung, Jayoun Kim, Young Min Cho, Kyung-Sang Yu, Joo-Youn Cho
Rosuvastatin is an HMG-CoA reductase inhibitor widely used for treating hypercholesterolaemia. We investigated whether genetic polymorphisms in solute carrier organic anion transporter 2B1 (SLCO2B1) affect the lipid-lowering effect of rosuvastatin in healthy adults with elevated low-density lipoprotein (LDL). This study included 18 volunteers with LDL levels above 130 mg/dL. Rosuvastatin (20 mg) was administered once a day for 8 weeks. Blood samples were drawn before and after the 8-week treatment to measure changes in lipid levels...
June 19, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/28594304/role-of-vitamin-d-pathway-gene-polymorphisms-on-rifampicin-plasma-and-intracellular-pharmacokinetics
#4
Sarah Allegra, Giovanna Fatiguso, Andrea Calcagno, Lorena Baietto, Ilaria Motta, Fabio Favata, Jessica Cusato, Stefano Bonora, Giovanni Di Perri, Antonio D'Avolio
AIM: We retrospectively evaluate the pharmacogenetic role of single nucleotide polymorphisms involved in rifampicin transport (SLCO1B1, MDR1 and PXR genes) and vitamin D (VDR, CYP24A1 and CYP27B1 genes) metabolism and activity on drug plasma and intracellular concentrations. PATIENTS & METHODS: Rifampicin Cmax and Ctrough were measured at weeks 2 and 4 using Ultra-Performance Liquid Chromatography-tandem mass spectroscopy methods. Allelic discrimination was performed by real-time polymerase chain reaction...
June 8, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28525903/polymorphisms-in-methotrexate-transporters-and-their-relationship-to-plasma-methotrexate-levels-toxicity-of-high-dose-methotrexate-and-outcome-of-pediatric-acute-lymphoblastic-leukemia
#5
Shu-Guang Liu, Chao Gao, Rui-Dong Zhang, Xiao-Xi Zhao, Lei Cui, Wei-Jing Li, Zhen-Ping Chen, Zhi-Xia Yue, Yuan-Yuan Zhang, Min-Yuan Wu, Jian-Xiang Wang, Zhi-Gang Li, Hu-Yong Zheng
High-dose methotrexate (HDMTX) plays an important role in the treatment of acute lymphoblastic leukemia (ALL) although there is great inter-patient variability in the efficacy and toxicity of MTX. The relationship between polymorphisms in genes encoding MTX transporters and MTX response is controversial. In the present study, 322 Chinese children with standard- and intermediate-risk ALL were genotyped for 12 polymorphisms. SLCO1B1 rs10841753 showed a significant association with plasma MTX levels at 48 h (P = 0...
June 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28524801/association-of-ugt2b7-ugt1a9-abcg2-and-il23r-polymorphisms-with-rejection-risk-in-kidney-transplant-patients
#6
Heloísa Lizotti Cilião, Rossana Batista Oliveira Camargo-Godoy, Marilesia Ferreira de Souza, Mariana Bisarro Dos Reis, Lorena Iastrenski, Vinicius Daher Alvares Delfino, Silvia Regina Rogatto, Ilce Mara de Syllos Cólus
Despite advances in testing compatibility between donor and recipient, graft rejection remains a current concern. Single-nucleotide polymorphisms (SNPs) that codify altered enzymes of metabolism, drug transport, and the immune system may contribute to graft rejection in transplant patients. This study examined the association between SNPs present in genes of these processes and occurrence of graft rejection episodes in 246 kidney transplant patients, 35% of which were diagnosed with rejection. Genotype-gene expression associations were also assessed...
May 19, 2017: Journal of Toxicology and Environmental Health. Part A
https://www.readbyqxmd.com/read/28482130/candidate-gene-study-of-functional-polymorphisms-in-slco1b1-and-cyp3a4-5-and-the-cholesterol-lowering-response-to-simvastatin
#7
J P Kitzmiller, J A Luzum, A Dauki, R M Krauss, M W Medina
Cholesterol-lowering response to 40 mg simvastatin daily for 6 weeks was examined for associations with common genetic polymorphisms in key genes affecting simvastatin metabolism (CYP3A4 and CYP3A5) and transport (SLCO1B1). In white people (n = 608), SLCO1B1 521C was associated with lesser reductions of total and low-density lipoprotein cholesterol. Associations between SLCO1B1 521C and cholesterol response were not detected in African Americans (n = 333). Associations between CYP3A4*22 or CYP3A5*3 and cholesterol response were not detected in either race, and no significant race-gene or gene-gene interactions were detected...
May 2017: Clinical and Translational Science
https://www.readbyqxmd.com/read/28461740/pharmacokinetic-interactions-between-glimepiride-and-rosuvastatin-in-healthy-korean-subjects-does-the-slco1b1-or-cyp2c9-genetic-polymorphism-affect-these-drug-interactions-observations-and-introspection-of-the-bioanalysis
#8
https://www.readbyqxmd.com/read/28461315/genetic-determinants-of-the-pharmacokinetic-variability-of-rifampin-in-malawian-adults-with-pulmonary-tuberculosis
#9
Derek J Sloan, Andrew D McCallum, Alessandro Schipani, Deirdre Egan, Henry C Mwandumba, Steve A Ward, David Waterhouse, Gertrude Banda, Theresa J Allain, Andrew Owen, Saye H Khoo, Geraint R Davies
Variable exposure to antituberculosis (TB) drugs, partially driven by genetic factors, may be associated with poor clinical outcomes. Previous studies have suggested an influence of the SLCO1B1 locus on the plasma area under the concentration-time curve (AUC) of rifampin. We evaluated the contribution of single nucleotide polymorphisms (SNPs) in SLCO1B1 and other candidate genes (AADAC and CES-1) to interindividual pharmacokinetic variability in Malawi. A total of 174 adults with pulmonary TB underwent sampling of plasma rifampin concentrations at 2 and 6 h postdose...
July 2017: Antimicrobial Agents and Chemotherapy
https://www.readbyqxmd.com/read/28435307/comparison-of-cyp2c9-cyp2c19-cyp2d6-abcb1-and-slco1b1-gene-polymorphism-frequency-in-russian-and-nanai-populations
#10
Dmitrij Alekseevitch Sychev, Grigorij Nikolaevich Shuev, Salavat Shejhovich Suleymanov, Kristina Anatol'evna Ryzhikova, Karin Badavievich Mirzaev, Elena Anatol'evna Grishina, Natalia Evgenievna Snalina, Zhannet Alimovna Sozaeva, Anton Mikhailovich Grabuzdov, Irina Andreevna Matsneva
BACKGROUND: The efficiency and safety of drug therapy depends on the peculiarities of functioning of the P450 cytochrome group and transporting proteins. There are significant differences for single-nucleotide polymorphism (SNP) frequency. MATERIALS AND METHODS: We studied the peculiarities of P450 cytochrome polymorphisms, SLCO1B1 transporting protein, and P-glycoprotein carriage in healthy volunteers in the Nanai ethnic group living in Russia, and compared them to the carriage of SNPs in the Russian population according to literature data...
2017: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/28435225/association-of-genetic-variations-with-pharmacokinetics-and-lipid-lowering-response-to-atorvastatin-in-healthy-korean-subjects
#11
Hye In Woo, Suk Ran Kim, Wooseong Huh, Jae-Wook Ko, Soo-Youn Lee
BACKGROUND: Statins are effective agents in the primary and secondary prevention of cardiovascular disease, but treatment response to statins varies among individuals. We analyzed multiple genetic polymorphisms and assessed pharmacokinetic and lipid-lowering responses after atorvastatin 80 mg treatment in healthy Korean individuals. METHODS: Atorvastatin 80 mg was given to 50 healthy Korean male volunteers. Blood samples were collected to measure plasma atorvastatin and lipid concentrations up to 48 hours after atorvastatin administration...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28429243/slco1b1-polymorphisms-and-plasma-estrone-conjugates-in-postmenopausal-women-with-er-%C3%A2-breast-cancer-genome-wide-association-studies-of-the-estrone-pathway
#12
Tanda M Dudenkov, James N Ingle, Aman U Buzdar, Mark E Robson, Michiaki Kubo, Irada Ibrahim-Zada, Anthony Batzler, Gregory D Jenkins, Tracy L Pietrzak, Erin E Carlson, Poulami Barman, Matthew P Goetz, Donald W Northfelt, Alvaro Moreno-Aspita, Clark V Williard, Krishna R Kalari, Yusuke Nakamura, Liewei Wang, Richard M Weinshilboum
BACKGROUND: Estrone (E1), the major circulating estrogen in postmenopausal women, promotes estrogen-receptor positive (ER+) breast tumor growth and proliferation. Two major reactions contribute to E1 plasma concentrations, aromatase (CYP19A1) catalyzed E1 synthesis from androstenedione and steroid sulfatase (STS) catalyzed hydrolysis of estrone conjugates (E1Cs). E1Cs have been associated with breast cancer risk and may contribute to tumor progression since STS is expressed in breast cancer where its activity exceeds that of aromatase...
April 20, 2017: Breast Cancer Research and Treatment
https://www.readbyqxmd.com/read/28397089/virtual-clinical-studies-to-examine-the-probability-distribution-of-the-auc-at-target-tissues-using-physiologically-based-pharmacokinetic-modeling-application-to-analyses-of-the-effect-of-genetic-polymorphism-of-enzymes-and-transporters-on-irinotecan-induced
#13
Kota Toshimoto, Atsuko Tomaru, Masakiyo Hosokawa, Yuichi Sugiyama
PURPOSE: To establish a physiologically-based pharmacokinetic (PBPK) model for analyzing the factors associated with side effects of irinotecan by using a computer-based virtual clinical study (VCS) because many controversial associations between various genetic polymorphisms and side effects of irinotecan have been reported. METHODS: To optimize biochemical parameters of irinotecan and its metabolites in the PBPK modeling, a Cluster Newton method was introduced...
April 10, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28391009/the-promise-of-pharmacogenomics-in-reducing-toxicity-during-acute-lymphoblastic-leukemia-maintenance-treatment
#14
REVIEW
Shoshana Rudin, Marcus Marable, R Stephanie Huang
Pediatric acute lymphoblastic leukemia (ALL) affects a substantial number of children every year and requires a long and rigorous course of chemotherapy treatments in three stages, with the longest phase, the maintenance phase, lasting 2-3years. While the primary drugs used in the maintenance phase, 6-mercaptopurine (6-MP) and methotrexate (MTX), are necessary for decreasing risk of relapse, they also have potentially serious toxicities, including myelosuppression, which may be life-threatening, and gastrointestinal toxicity...
April 2017: Genomics, Proteomics & Bioinformatics
https://www.readbyqxmd.com/read/28385543/rosuvastatin-pharmacokinetics-in-asian-and-white-subjects-wild-type-for-both-oatp1b1-and-bcrp-under-control-and-inhibited-conditions
#15
Hsin-Fang Wu, Nadya Hristeva, Jae Chang, Xiaorong Liang, Ruina Li, Lynda Frassetto, Leslie Z Benet
The FDA recommends rosuvastatin dosage reductions in Asian patients because pharmacokinetic studies have demonstrated an approximate two-fold increase in median exposure to rosuvastatin in Asian subjects when compared to Caucasian controls. Yet, no explanation for this ethnic difference has been confirmed. Here we show that rosuvastatin exposure in Asians and Whites does not differ significantly when all subjects are wildtype carriers for both Solute Carrier Organic anion transporter1B1 *1a and ATP Binding Cassette Subfamily G Member 2 c...
April 3, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28350522/the-influences-of-slco1b1-and-abcb1-genotypes-on-the-pharmacokinetics-of-simvastatin-in-relation-to-cyp3a4-inhibition
#16
Fen Jiang, Jong-Yeol Choi, Ju-Hyun Lee, Sunae Ryu, Ze-Won Park, Jong-Gu Lee, Han-Sung Na, Seok-Yong Lee, Woo-Yong Oh, Myeon-Woo Chung, Seung-Eun Choi
AIM: To investigate the combined effects of SLCO1B1 and ABCB1 genotypes on the pharmacokinetics of simvastatin and its active metabolite simvastatin acid, in relation to CYP3A4 inhibition. METHODS: We conducted a single-dose pharmacokinetic study of simvastatin in 26 healthy volunteers screened for their SLCO1B1 c.521T>C and ABCB1 c.1236C>T-2677G>T-3435C>T genotypes, with and without amlodipine pretreatment. The genetic effects and drug-interaction effect on simvastatin pharmacokinetic parameters were analyzed using a linear-mixed model...
April 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28260863/pharmacokinetic-interactions-between-glimepiride-and-rosuvastatin-in-healthy-korean-subjects-does-the-slco1b1-or-cyp2c9-genetic-polymorphism-affect-these-drug-interactions
#17
RANDOMIZED CONTROLLED TRIAL
Choon Ok Kim, Eun Sil Oh, Hohyun Kim, Min Soo Park
To improve cardiovascular outcomes, dyslipidemia in patients with diabetes needs to be treated. Thus, these patients are likely to take glimepiride and rosuvastatin concomitantly. Therefore, this study aimed to evaluate the pharmacokinetic (PK) interactions between these two drugs in healthy males and to explore the effect of SLCO1B1 and CYP2C9 polymorphisms on their interactions in two randomized, open-label crossover studies. Glimepiride was studied in part 1 and rosuvastatin in part 2. Twenty-four participants were randomly assigned to each part...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28252633/-use-of-pharmacogenetic-testing-to-prevent-adverse-drug-reactions-during-statin-therapy
#18
REVIEW
N A Rumyantsev, V G Kukes, R E Kazakov, A A Rumyantsev, D A Sychev
The number of patients receiving statins increases every year and due to the fact that they should take statins during their lives, the problem of their safety use comes to the forefront. The paper analyzes the safety of using the medications of this group and discusses the diagnosis of myopathies induced by statins and the occurrence of immune-mediated statin myopathies. It considers a personalized approach to prescribing statins, analyzes Russian and foreign experience in using pharmacogenetics to reduce the risk of myopathies, publishes the results of the authors' experience in clinically introducing pharmacogenetic testing at hospitals, and analyzes the long-term results of determining the polymorphism of the SLCO1B1 gene for the prediction of the risk of adverse events when using statins and estimating patient compliance to prescribed treatment...
2017: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/28225057/intracellular-drug-bioavailability-a-new-predictor-of-system-dependent-drug-disposition
#19
André Mateus, Andrea Treyer, Christine Wegler, Maria Karlgren, Pär Matsson, Per Artursson
Intracellular drug exposure is influenced by cell- and tissue-dependent expression of drug-transporting proteins and metabolizing enzymes. Here, we introduce the concept of intracellular bioavailability (Fic) as the fraction of extracellular drug available to bind intracellular targets, and we assess how Fic is affected by cellular drug disposition processes. We first investigated the impact of two essential drug transporters separately, one influx transporter (OATP1B1; SLCO1B1) and one efflux transporter (P-gp; ABCB1), in cells overexpressing these proteins...
February 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28157071/association-between-abcg2-and-slco1b1-polymorphisms-and-adverse-drug-reactions-to-regorafenib-a-preliminary-study%C3%A2
#20
Akimitsu Maeda, Hitoshi Ando, Takashi Ura, Azusa Komori, Ayako Hasegawa, Hiroya Taniguchi, Shigenori Kadowaki, Kei Muro, Masahiro Tajika, Makiko Kobara, Masahide Matsuzaki, Naoya Hashimoto, Mieko Maeda, Yasushi Kojima, Masahiro Aoki, Eisaku Kondo, Akiyoshi Mizutani, Akio Fujimura
OBJECTIVE: Due to the occurrence of severe adverse drug reactions to regorafenib, a drug used in cancer therapy, the identification of a predictive marker(s) is needed to increase the therapeutic applicability of this compound. We therefore investigated whether polymorphisms in the <i>ABCG2</i> and <i>SLCO1B</i> genes are associated with adverse drug reactions to regorafenib. METHODS: For these analyses, 37 Japanese cancer patients were treated with regorafenib, genotyped for polymorphisms in <i>ABCG2</i> and <i>SLCO1B</i>, and evaluated for drug-related adverse drug reactions...
May 2017: International Journal of Clinical Pharmacology and Therapeutics
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