Association of genetic polymorphisms in the influx transporter SLCO1B3 and the efflux transporter ABCB1 with imatinib pharmacokinetics in patients with chronic myeloid leukemia.


:This study explored the association of 14 single nucleotide polymorphisms in three genes coding for influx transporters (SLC22A1, SLCO1B1, and SLCO1B3), two genes coding for efflux transporters (ABCB1 and ABCG2), and four genes coding for enzymes (CYP2C9, CYP2C19, CYP2D6, and CYP3A5) with the pharmacokinetics of imatinib in Japanese patients with chronic myeloid leukemia. Pharmacokinetic parameters were estimated by a population pharmacokinetic analysis based on 622 plasma samples from 34 patients at steady state. Approximately 4.6-fold variability in individual clearance was observed (range, 3.4-15.5 L/hr). The individual estimated clearance was significantly increased in patients with the SLCO1B3 334GG genotype (median value ± standard deviation, 9.5 ± 3.1 L/hr; n = 19) compared with SLCO1B3 334TT and TG genotypes (7.0 ± 3.1 L/hr; n = 15) (P = 0.019). Patients with the ABCB1 3435CC genotype had significantly higher imatinib clearance (12.7 ± 3.0 L/hr; n = 7) compared with patients with ABCB1 3435CT and TT genotypes (7.9 ± 2.7 L/hr; n = 27) (P = 0.035). In conclusion, the present study suggests that single nucleotide polymorphisms of the influx transporter SLCO1B3 and the efflux transporter ABCB1 were functionally associated with individual variability of imatinib pharmacokinetics in Japanese patients with chronic myeloid leukemia.


Ther Drug Monit


Yamakawa Y,Hamada A,Nakashima R,Yuki M,Hirayama C,Kawaguchi T,Saito H




Has Abstract


2011-04-01 00:00:00












  • Old and new antirheumatic drugs and the risk of hepatotoxicity.

    abstract::Given the high prevalence of the use of medications in daily practice and the large number of people taking antirheumatic agents, the risk of drug-drug interactions and of hepatotoxicity is of concern. Both old and new compounds show such a risk. Nonsteroidal antinflammatory drugs are widely used drugs with potential ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,评审


    authors: Anelli MG,Scioscia C,Grattagliano I,Lapadula G

    更新日期:2012-12-01 00:00:00

  • Mycophenolic acid interaction with cyclosporine and tacrolimus in vitro and in vivo: evaluation of additive effects on rat blood lymphocyte function.

    abstract::The effect of mycophenolic acid (MPA) in combination with either cyclosporine (CsA) or tacrolimus (TRL) on whole-blood lymphocyte function was assessed in vitro as well as in vivo. For the in vitro studies, rat whole blood was incubated with different concentrations of MPA together with CsA or TRL. In vivo, rats (n = ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Barten MJ,Shipkova M,Bartsch P,Dhein S,Streit F,Tarnok A,Armstrong VW,Mohr FW,Oellerich M,Gummert JF

    更新日期:2005-04-01 00:00:00

  • Carbamazepine and its epoxide: an open study of efficacy and side effects after carbamazepine dose increment in refractory partial epilepsy.

    abstract::We evaluated the efficacy, development of adverse effects, and possible correlation between the plasma concentration of carbamazepine (CBZ) and its major metabolite, carbamazepine-10,11-epoxide (CBZ-E), in a group of epileptic patients in whom selective increases in CBZ doses were made. Eighteen patients with refracto...

    journal_title:Therapeutic drug monitoring

    pub_type: 临床试验,杂志文章


    authors: Semah F,Gimenez F,Longer E,Laplane D,Thuillier A,Baulac M

    更新日期:1994-12-01 00:00:00

  • Comprehensive drug screening by integrated use of gas chromatography/mass spectrometry and Remedi HS.

    abstract::The authors evaluated an integrated approach for the screening of drugs in biosamples consisting of gas chromatography/mass spectrometry analysis of serum or whole blood (SB/GC-MS) and of high-performance liquid chromatographic and ultraviolet (HPLC-UV) analysis of urine with the REMEDi HS Biorad system (U/REM) (Bio-r...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Valli A,Polettini A,Papa P,Montagna M

    更新日期:2001-06-01 00:00:00

  • Comparison of bioassay, high-performance liquid chromatography, and fluorescence polarization immunoassay for quantitative determination of vancomycin in serum.

    abstract::This investigation was designed to compare three assay techniques, the traditional bioassay (agar diffusion), and two more recent techniques, high-performance liquid chromatography (HPLC) and fluorescence polarization immunoassay (FPIA), for the determination of vancomycin concentrations in serum. One hundred clinical...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Ristuccia PA,Ristuccia AM,Bidanset JH,Cunha BA

    更新日期:1984-01-01 00:00:00

  • Clinical use of a simultaneous HPLC assay for indinavir, saquinavir, ritonavir and nelfinavir in children and adults.

    abstract::PROTEASE INHIBITOR TDM: This study examines the importance of therapeutic drug monitoring (TDM) of protease inhibitors (PI) in adults and children infected with the human immunodeficiency virus (HIV). Pediatric patients were included because information in this population is limited. A high performance liquid chromato...

    journal_title:Therapeutic drug monitoring

    pub_type: 更正并重新发布的文章,杂志文章


    authors: Walson PD,Cox S,Utkin I,Gerber N,Crim L,Brady M,Koranyi K

    更新日期:2003-12-01 00:00:00

  • Simultaneous plasma carbamazepine and carbamazepine-epoxide concentrations in pharmacokinetic and bioavailability studies.

    abstract::A comparative bioavailability study of carbamazepine (CBZ) in tablets and a syrup preparation was carried out in six volunteers, using a crossover design. Plasma and saliva samples were collected at appropriate times, and the plasma specimens were analyzed by high performance liquid chromatography for concentrations o...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Hooper WD,King AR,Patterson M,Dickinson RG,Eadie MJ

    更新日期:1985-01-01 00:00:00

  • Poor performance of laboratories assaying newly developed antiretroviral agents: results for darunavir, etravirine, and raltegravir from the international quality control program for therapeutic drug monitoring of antiretroviral drugs in human plasma/seru

    abstract:BACKGROUND:The International Interlaboratory Quality Control PROGRAM for Therapeutic Drug Monitoring of Antiretroviral Drugs in Human Plasma/Serum was initiated in 1999. We have previously published our experience during the first 10 years of the PROGRAM. Since 2010, 3 newly developed antiretroviral agents have been ad...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Burger D,Krens S,Robijns K,Aarnoutse R,Brüggemann R,Touw D

    更新日期:2014-12-01 00:00:00

  • Validation of a Capillary Dry Blood Sample MITRA-Based Assay for the Quantitative Determination of Systemic Tacrolimus Concentrations in Transplant Recipients.

    abstract:BACKGROUND:Tacrolimus is a narrow therapeutic index medication, which requires therapeutic drug monitoring to optimize dosing based on systemic exposure. MITRA microsampling offers a convenient, minimally invasive approach for the collection of capillary blood samples from a fingerprick versus conventional venous blood...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Undre N,Dawson I,Aluvihare V,Kamar N,Saliba F,Torpey N,Anaokar S,Kazeem G,Hussain I

    更新日期:2020-12-03 00:00:00

  • Screening procedure for detection of diuretics and uricosurics and/or their metabolites in human urine using gas chromatography-mass spectrometry after extractive methylation.

    abstract::A gas chromatography-mass spectrometry (GC-MS)-based screening procedure was developed for the detection of diuretics, uricosurics, and/or their metabolites in human urine after extractive methylation. Phase-transfer catalyst remaining in the organic phase was removed by solid-phase extraction on a diol phase. The com...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Beyer J,Bierl A,Peters FT,Maurer HH

    更新日期:2005-08-01 00:00:00

  • Evaluation of MPA and MPAG removal by continuous venovenous hemodiafiltration and continuous venovenous hemofiltration.

    abstract::The study assessed the removal of mycophenolic acid (MPA) and its major glucuronide metabolite (MPAG) during continuous venovenous hemofiltration (CVVHF) and continuous venovenous hemodiafiltration (CVVHDF) in 4 heart transplant recipients treated for at least 6 days with mycophenolate mofetil (MMF) in addition to cyc...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Cussonneau X,Bolon-Larger M,Prunet-Spano C,Bastien O,Boulieu R

    更新日期:2008-02-01 00:00:00

  • Polymorphisms in CYP3A5, CYP3A4, and ABCB1 are not associated with cyclosporine pharmacokinetics nor with cyclosporine clinical end points after renal transplantation.

    abstract:BACKGROUND:The association of CYP3A5, CYP3A4, and ABCB1 single nucleotide polymorphisms (SNPs) with cyclosporine (CsA) pharmacokinetics is controversial. The authors studied the influence of these SNPs on CsA pharmacokinetics as well as on the incidence of biopsy-proven acute rejection (BPAR) and renal function after k...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Bouamar R,Hesselink DA,van Schaik RH,Weimar W,Macphee IA,de Fijter JW,van Gelder T

    更新日期:2011-04-01 00:00:00

  • Stability of tacrolimus (FK 506) and cyclosporin G in whole blood.

    abstract::The stability of two new immunosuppressants, tacrolimus and cyclosporin G (CsG), was evaluated in whole blood following incubation of patient specimens at ambient temperature or 4 degrees C for time periods of 2 (48 h) and 7 days (168 h) after collection. No decrease in CsG concentrations was noted over a 7-day period...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Annesley TM,Hunter BC,Fidler DR,Giacherio DA

    更新日期:1995-08-01 00:00:00

  • A clinically useful capillary blood-sampling technique for rapid determination of therapeutic levels of theophylline.

    abstract::Two blood-sampling techniques, capillary and venous, were compared using the EMIT method. No difference was found in reproducibility. However, persistent positive bias of 0.628 micrograms/ml (p less than 0.01) was noted with the capillary sampling method. Any hemolysis that occurred in the capillary sampling technique...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Frazer JF 3rd,Stasiowski P,Boyd GK

    更新日期:1983-01-01 00:00:00

  • Dasatinib, a multikinase inhibitor: therapy, safety, and appropriate management of adverse events.

    abstract::Tyrosine kinase inhibitors are the standard of care for the treatment of chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia. Dasatinib is a second-generation tyrosine kinase inhibitor that has been shown to be efficacious in treatment of patients with chronic myeloid leukemia or ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,评审


    authors: Shayani S

    更新日期:2010-12-01 00:00:00

  • Impact of Laboratory Practices on Interlaboratory Variability in Therapeutic Drug Monitoring of Immunosuppressive Drugs.

    abstract::The immunosuppressants cyclosporine, tacrolimus, sirolimus, everolimus, and probably also mycophenolic acid require therapeutic drug monitoring (TDM)-guided dosing to ensure that blood concentrations are kept within the target range in transplant patients. Reliable, accurate, and precise test methods are therefore ess...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Christians U,Vinks AA,Langman LJ,Clarke W,Wallemacq P,van Gelder T,Renjen V,Marquet P,Meyer EJ

    更新日期:2015-12-01 00:00:00

  • Determination of rapamycin in whole blood by HPLC.

    abstract::Sirolimus (rapamycin, RAPA) is a natural fermentation product (macrolide antibiotic) that has demonstrated potent immunosuppressive activity. A reverse-phase high-performance liquid chromatographic (HPLC) method is described for analysis of the drug in whole blood. The samples are purified by using liquid-liquid extra...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Svensson JO,Brattström C,Säwe J

    更新日期:1997-02-01 00:00:00

  • Clinical correlates of methylphenidate blood levels.

    abstract::The clinical correlates of methylphenidate blood levels in hyper-active children and normal adults were examined in five studies. Although occasional correlations between blood levels and neuroendocrine response were noted within subjects along the pharmacokinetic time profile of the drug, no significant associations ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Gualtieri CT,Hicks RE,Patrick K,Schroeder SR,Breese GR

    更新日期:1984-01-01 00:00:00

  • Determination of linezolid in human plasma by high-performance liquid chromatography with ultraviolet detection.

    abstract::A high-performance liquid chromatographic method for the determination of linezolid in human plasma was developed and validated. After precipitation of plasma proteins with perchloric acid, the protein-free supernatant was separated by isocratic reverse-phase chromatography on a X Bridge C18 column. The mobile phase c...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Cattaneo D,Baldelli S,Conti F,Cozzi V,Clementi E

    更新日期:2010-08-01 00:00:00

  • Pharmacokinetic drug interaction potential of risperidone with cytochrome p450 isozymes as assessed by the dextromethorphan, the caffeine, and the mephenytoin test.

    abstract::Two published case reports showed that addition of risperidone (1 and 2 mg/d) to a clozapine treatment resulted in a strong increase of clozapine plasma levels. As clozapine is metabolized by cytochrome P450 isozymes, a study was initiated to assess the in vivo interaction potential of risperidone on various cytochrom...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Eap CB,Bondolfi G,Zullino D,Bryois C,Fuciec M,Savary L,Jonzier-Perey M,Baumann P

    更新日期:2001-06-01 00:00:00

  • Pharmacokinetics and pharmacodynamics of methadone enantiomers in hospice patients with cancer pain.

    abstract::Racemic methadone is increasingly used to manage cancer pain. The authors studied 13 terminally ill patients with cancer pain, who underwent switching (rotation) from morphine to methadone. The relationship between initial morphine dose and final methadone dose, the pharmacokinetics of R- and S- methadone, and the deg...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Auret K,Roger Goucke C,Ilett KF,Page-Sharp M,Boyd F,Oh TE

    更新日期:2006-06-01 00:00:00

  • Therapeutic drug monitoring reduces toxic drug reactions: a meta-analysis.

    abstract::Therapeutic drug monitoring (TDM) is commonly employed to optimize the dosing of certain drugs, including digoxin, aminoglycosides, theophylline, and phenytoin. Studies were reviewed in order to (a) evaluate the effect of TDM on the occurrence of toxic drug reactions (TDRs) and (b) identify factors that may modify or ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,meta分析


    authors: Ried LD,Horn JR,McKenna DA

    更新日期:1990-01-01 00:00:00

  • Determination of cefsulodin in biological fluids by high-pressure liquid chromatography.

    abstract::Cefsulodin is a third-generation cephalosporin with a unique specificity for Pseudomonas aeruginosa. To study the pharmacokinetics of this agent in children, a rapid and sensitive high-performance liquid chromatographic micromethod was developed for plasma and urine. Protein was precipitated from plasma with one volum...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Ackers IM,Myers CM,Blumer JL

    更新日期:1984-01-01 00:00:00

  • Therapeutic Drug Monitoring for Perampanel in Japanese Epilepsy Patients: Influence of Concomitant Antiepileptic Drugs.

    abstract:BACKGROUND:Perampanel is a new antiepileptic drug (AED) that acts as a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor antagonist and is mainly metabolized by cytochrome P450 (CYP) 3A4. This study evaluated the influence of concomitant AEDs on the serum concentration profile of pera...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Yamamoto Y,Usui N,Nishida T,Takahashi Y,Imai K,Kagawa Y,Inoue Y

    更新日期:2017-08-01 00:00:00

  • Tacrolimus Exposure in Obese Patients: A Case-Control Study in Kidney Transplantation.

    abstract:BACKGROUND:Tacrolimus pharmacokinetics in obese patients have been poorly studied. Herein, the authors explored the impact of obesity on tacrolimus exposure in kidney transplant recipients (KTRs) and estimated a more suitable initial dosage in this population. METHODS:A retrospective, observational, monocentric case-c...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Robert V,Manos-Sampol E,Manson T,Robert T,Decourchelle N,Anne-Sophie G,Quaranta S,Moal V,Legris T

    更新日期:2020-10-05 00:00:00

  • Therapeutic drug monitoring of common antipsychotics.

    abstract::The aim of this review is to provide information for interpreting outcome results from monitoring of antipsychotics in biological samples. A brief overview of the working mechanisms, pharmacological effects, drug interactions, and analytical methods of classical and atypical antipsychotics is given. Nineteen antipsych...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,评审


    authors: Patteet L,Morrens M,Maudens KE,Niemegeers P,Sabbe B,Neels H

    更新日期:2012-12-01 00:00:00

  • Theophylline clearance during and after mild upper respiratory infection.

    abstract::Theophylline clearance was estimated by a single-sample technique in 19 subjects with acute clinical respiratory infections. Mean (+/- SD) theophylline clearance during acute illness was 0.044 +/- 0.011 L X h-1 X kg-1 compared to 0.043 +/- 0.012 L X h-1 X kg-1 1 month later. In a subset of five subjects, single-sample...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Bachmann K,Schwartz J,Martin M,Jauregui L

    更新日期:1987-09-01 00:00:00

  • Evidence of polymorphic CYP2C19 involvement in the human metabolism of N-desmethylclobazam.

    abstract::The authors report preliminary findings on the potential contribution of CYP2C19 isoenzyme to the human metabolism of N-desmethylclobazam (N-CLB), the main active metabolite of clobazam (CLB), a benzodiazepine frequently used as add-on therapy in patients with refractory epilepsy. Two children on CLB treatment showing...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Contin M,Sangiorgi S,Riva R,Parmeggiani A,Albani F,Baruzzi A

    更新日期:2002-12-01 00:00:00

  • Therapeutic Drug Monitoring Can Improve Linezolid Dosing Regimens in Current Clinical Practice: A Review of Linezolid Pharmacokinetics and Pharmacodynamics.

    abstract::Linezolid is an antibiotic used to treat infections caused by drug-resistant gram-positive organisms, including vancomycin-resistant Enterococcus faecium, multi-drug resistant Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus. The adverse effects of linezolid can include thrombocytopenia and ne...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Rao GG,Konicki R,Cattaneo D,Alffenaar JW,Marriott DJE,Neely M,IATDMCT Antimicrobial Scientific Committee.

    更新日期:2020-02-01 00:00:00

  • Clinical Practice Recommendations for the Management and Prevention of Cisplatin-Induced Hearing Loss Using Pharmacogenetic Markers.

    abstract::Currently no pharmacogenomics-based criteria exist to guide clinicians in identifying individuals who are at risk of hearing loss from cisplatin-based chemotherapy. This review summarizes findings from pharmacogenomic studies that report genetic polymorphisms associated with cisplatin-induced hearing loss and aims to ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,评审


    authors: Lee JW,Pussegoda K,Rassekh SR,Monzon JG,Liu G,Hwang S,Bhavsar AP,Pritchard S,Ross CJ,Amstutz U,Carleton BC,CPNDS Clinical Recommendations Group.

    更新日期:2016-08-01 00:00:00