Abstract:
OBJECTIVES:The effect of rifapentine plus isoniazid on efavirenz pharmacokinetics was characterized in AIDS Clinical Trials Group protocol A5279 (NCT01404312). The present analyses characterize pharmacogenetic interactions between these drugs, and with nevirapine. METHODS:A subset of HIV-positive individuals receiving efavirenz- or nevirapine-containing antiretroviral therapy in A5279 underwent pharmacokinetic evaluations at baseline, and again weeks 2 and 4 after initiating daily rifapentine plus isoniazid. Associations with polymorphisms relevant to efavirenz, nevirapine, isoniazid, and rifapentine pharmacokinetics were assessed. RESULTS:Of 128 participants, 101 were evaluable for associations with rifapentine and its active 25-desacetyl metabolite, 87 with efavirenz, and 38 with nevirapine. In multivariable analyses, NAT2 slow acetylators had greater week 4 plasma concentrations of rifapentine (P = 2.6 × 10) and 25-desacetyl rifapentine (P = 7.0 × 10) among all participants, and in efavirenz and nevirapine subgroups. NAT2 slow acetylators also had greater plasma efavirenz and nevirapine concentration increases from baseline to week 4, and greater decreases from baseline in clearance. CYP2B6 poor metabolizers had greater efavirenz concentrations at all weeks and greater nevirapine concentrations at baseline. None of 47 additional polymorphisms in 11 genes were significantly associated with pharmacokinetics. CONCLUSIONS:Among HIV-positive individuals receiving efavirenz or nevirapine, and who then initiated rifapentine plus isoniazid in A5279, NAT2 slow acetylators had greater rifapentine and 25-desacetyl rifapentine concentrations, and greater increases from baseline in plasma efavirenz and nevirapine concentrations. These associations are likely mediated by greater isoniazid exposure in NAT2 slow acetylators.
journal_name
Pharmacogenet Genomicsjournal_title
Pharmacogenetics and genomicsauthors
Haas DW,Podany AT,Bao Y,Swindells S,Chaisson RE,Mwelase N,Supparatpinyo K,Mohapi L,Gupta A,Benson CA,Baker P,Fletcher CVdoi
10.1097/FPC.0000000000000417subject
Has Abstractpub_date
2021-01-01 00:00:00pages
17-27issue
1eissn
1744-6872issn
1744-6880journal_volume
31pub_type
杂志文章abstract::We have identified the ATP-binding cassette (ABC) transporter ABCC4 as an active constituent of mediator-storing granules in human platelets. In addition to multidrug resistance protein 4, other ABC-type transport proteins may contribute to platelet secretory function as well as determine intended or adverse effects o...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e32833997b0
更新日期:2010-06-01 00:00:00
abstract::The aryl hydrocarbon receptor (AhR) is a key regulator of the transcriptional expression for the cytochrome P450 1 (CYP1) genes. CYP1A2 is one of the major CYP1 enzymes that catalyse 2-hydroxylation of estrogen, a hormone that plays a critical role in the etiology of breast cancer. In this study, we investigated wheth...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/01.fpc.0000189803.34339.ed
更新日期:2006-04-01 00:00:00
abstract:OBJECTIVE:To determine whether polymorphisms in the sulfonamide detoxification genes, CYB5A (encoding cytochrome b(5)), CYB5R3 (encoding cytochrome b(5) reductase), or NAT2 (encoding N-acetyltransferase 2) were over-represented in patients with delayed sulfonamide drug hypersensitivity, compared with control patients w...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328357a735
更新日期:2012-10-01 00:00:00
abstract:OBJECTIVE:Clinical response to topiramate can vary greatly in obese patients. Identifying genetic variants associated with treatment response could help gain insight into the mechanism of action of topiramate. Little is known about the relationship between genetic variability and topiramate treatment response. We perfo...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000185
更新日期:2016-02-01 00:00:00
abstract::Several novel single nucleotide polymorphisms (SNPs) involved in cytarabine cytotoxicity and related to clinical outcomes have been reported recently in a series of 232 pediatric patients with acute myeloid leukemia (AML). We report the first adult AML cohort in which the influence of these SNPs in cytarabine efficacy...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000286
更新日期:2017-07-01 00:00:00
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journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e3283395c6a
更新日期:2010-05-01 00:00:00
abstract::Heterotrimeric guanine-binding proteins (G proteins) transmit signals from the cell surface to intracellular signal cascades. The β3-subunit encoded by the gene GNB3 is widely expressed and, therefore, involved in various physiological and pathophysiological processes. A C825T polymorphism located in exon 10 of GNB3 w...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章,评审
doi:10.1097/FPC.0b013e3283491153
更新日期:2011-09-01 00:00:00
abstract:OBJECTIVE:To test the hypothesis that the two nonsynonymous single nucleotide polymorphisms at the CB2 cannabinoid receptor gene may have functional consequences on human CB2. METHODS:Q63R, H316Y, and Q63R/H316 mutations were made in recombinant human CB2 by the method of site-directed mutagenesis. After these mutant ...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e3283367c6b
更新日期:2010-03-01 00:00:00
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journal_title:Pharmacogenetics and genomics
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doi:10.1097/01.fpc.0000220571.20961.dd
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doi:10.1097/FPC.0000000000000251
更新日期:2017-01-01 00:00:00
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journal_title:Pharmacogenetics and genomics
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doi:10.1097/FPC.0000000000000267
更新日期:2017-04-01 00:00:00
abstract::A possible association between the combination of genetic variations in hepatocyte nuclear factor 4α (HNF4α) and constitutive androstane receptor (CAR) and the stable doses of warfarin was examined in patients from the Ewha-Severance Treatment (EAST) Group of Warfarin. Around 42.5% of the overall interindividual varia...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000103
更新日期:2015-01-01 00:00:00
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doi:10.1097/FPC.0b013e328335731c
更新日期:2010-03-01 00:00:00
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journal_title:Pharmacogenetics and genomics
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:2009-06-01 00:00:00
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journal_title:Pharmacogenetics and genomics
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doi:10.1097/FPC.0000000000000163
更新日期:2015-11-01 00:00:00
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journal_title:Pharmacogenetics and genomics
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doi:10.1097/FPC.0b013e3282fc5801
更新日期:2008-06-01 00:00:00
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journal_title:Pharmacogenetics and genomics
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更新日期:2014-05-01 00:00:00
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journal_title:Pharmacogenetics and genomics
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doi:10.1097/FPC.0b013e3283117d79
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journal_title:Pharmacogenetics and genomics
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journal_title:Pharmacogenetics and genomics
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doi:10.1097/FPC.0b013e32834e3572
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journal_title:Pharmacogenetics and genomics
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doi:10.1097/FPC.0b013e3283493a23
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journal_title:Pharmacogenetics and genomics
pub_type: 临床试验,杂志文章
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更新日期:2010-12-01 00:00:00
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journal_title:Pharmacogenetics and genomics
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doi:10.1097/FPC.0b013e328350012b
更新日期:2012-03-01 00:00:00
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journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0b013e328349daa1
更新日期:2011-11-01 00:00:00
abstract:OBJECTIVE:The effects of CYP2C9*1/*3 and *3/*3 genotypes on the pharmacokinetics and pharmacodynamics of meloxicam were evaluated in healthy Korean subjects. METHODS:After oral administration of 15 mg meloxicam, the plasma concentrations of meloxicam were assessed in 11 CYP2C9*1/*1 individuals, eight CYP2C9*1/*3 indiv...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000025
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journal_title:Pharmacogenetics and genomics
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更新日期:2011-03-01 00:00:00
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journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
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更新日期:2016-02-01 00:00:00
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journal_title:Pharmacogenetics and genomics
pub_type: 临床试验,杂志文章
doi:10.1097/01.fpc.0000230412.89973.c0
更新日期:2006-11-01 00:00:00
abstract:BACKGROUND/AIM:MicroRNAs (miRNAs) are small noncoding RNAs that have been implicated in mechanisms underlying various types of cancers including hepatocellular carcinoma (HCC). Reports have indicated that single nucleotide polymorphisms in miRNA-196A2 and miRNA-146A genes may contribute to the risk of progression of he...
journal_title:Pharmacogenetics and genomics
pub_type: 杂志文章
doi:10.1097/FPC.0000000000000187
更新日期:2016-02-01 00:00:00