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












  • A comparison of venous versus capillary measurements of drug concentration.

    abstract::Accessing patient's veins for drug level sampling is not always feasible. The use of capillary sampling techniques is often utilized when venous access is hampered. In the therapeutic monitoring of patients, unexpected drug level results often occur that can be caused by a number of different factors. The possibility ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Murphy JE,Peltier T,Anderson D,Ward ES

    更新日期:1990-05-01 00:00:00

  • Evaluation of caffeine as an in vivo probe for CYP1A2 using measurements in plasma, saliva, and urine.

    abstract::Twenty-five healthy volunteers were given 100 mg caffeine orally and several estimates of cytochrome P450 1A2 (CYP1A2) activity were evaluated. The validation was performed by correlation of different parameters in plasma, saliva, and urine to two measures of caffeine clearance, CL(oral) and CL(137X-->17X) that served...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Carrillo JA,Christensen M,Ramos SI,Alm C,Dahl ML,Benitez J,Bertilsson L

    更新日期:2000-08-01 00:00:00

  • Impact of POR and CYP3A5 Polymorphisms on Trough Concentration to Dose Ratio of Tacrolimus in the Early Post-operative Period Following Kidney Transplantation.

    abstract:BACKGROUND:Tacrolimus, a critical dose drug, is widely used in transplantation. Knowing the contribution of genetic factors, which significantly influence tacrolimus variability, is beneficial in the personalization of its starting dose. The significant impact of CYP3A5*3 polymorphisms on tacrolimus exposure has been r...

    journal_title:Therapeutic drug monitoring

    pub_type: 临床试验,杂志文章


    authors: Phupradit A,Vadcharavivad S,Ingsathit A,Kantachuvesiri S,Areepium N,Sra-Ium S,Auamnoy T,Sukasem C,Sumethkul V,Kitiyakara C

    更新日期:2018-10-01 00:00:00

  • Population Pharmacokinetic Analysis of Phenytoin After Intravenous Administration of Fosphenytoin in Adult and Elderly Epileptic Patients.

    abstract:BACKGROUND:Fosphenytoin, the diphosphate ester salt of phenytoin, is widely used to treat status epilepticus. The aim of this study was to develop a population pharmacokinetic (PPK) model to describe serum phenytoin concentrations after the intravenous administration of fosphenytoin in adult and elderly epileptic patie...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Higuchi K,Yamashita D,Kashihara Y,Kakara M,Hirota T,Hirakawa M,Ieiri I

    更新日期:2019-10-01 00:00:00

  • Limited sampling strategies for therapeutic drug monitoring of mycophenolate mofetil therapy in patients with autoimmune disease.

    abstract::Mycophenolate mofetil (MMF) is increasingly used for the treatment of autoimmune diseases (AID). In renal transplant recipients, it has been demonstrated that adjustment of the MMF dose according to the area under the plasma concentration versus time curve (AUC) of mycophenolic acid (MPA), the active moiety of MMF, im...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: de Winter BC,Neumann I,van Hest RM,van Gelder T,Mathot RA

    更新日期:2009-06-01 00:00:00

  • No pharmacokinetic but pharmacodynamic interactions between cisapride and bromperidol or haloperidol.

    abstract::Pharmacokinetic and pharmacodynamic interactions between the gastrokinetic drug cisapride and the antipsychotic drugs bromperidol and haloperidol were studied in 29 schizophrenic inpatients. Fourteen patients were taking bromperidol (12-24 mg/d), and 15 were taking haloperidol (12-36 mg/d). Cisapride 10 mg/d was coadm...

    journal_title:Therapeutic drug monitoring

    pub_type: 临床试验,杂志文章


    authors: Mihara K,Otani K,Yasui N,Ishida M,Kondo T,Suzuki A,Furukori H,Nagashima U,Kaneko S,Inoue Y

    更新日期:1999-06-01 00:00:00

  • The effect of coadministration of duloxetine on steady-state serum concentration of risperidone and aripiprazole: a study based on therapeutic drug monitoring data.

    abstract::Previous studies have categorized duloxetine as a moderate inhibitor of CYP2D6. The aim of the present study was to investigate the potential interactions between duloxetine and the two CYP2D6 substrates risperidone and aripiprazole in psychiatric patients. Serum concentration data from patients treated with risperido...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Hendset M,Molden E,Enoksen TB,Refsum H,Hermann M

    更新日期:2010-12-01 00:00:00

  • Cyclosporin A trough levels correlate with serum lipoproteins and apolipoproteins: implications for therapeutic drug monitoring of cyclosporin A.

    abstract::In a prospective study over 6 months, the relationship between serum lipid parameters and CsA whole blood trough concentrations was investigated in 39 renal transplant recipients receiving a triple immunosuppressive therapy with cyclosporin (CsA), azathioprine and prednisone. CsA trough concentrations were measured wi...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: von Ahsen N,Helmhold M,Schütz E,Eisenhauer T,Armstrong VW,Oellerich M

    更新日期:1997-04-01 00:00:00

  • Identification of uridine diphosphate glucuronosyltransferases involved in the metabolism and clearance of mycophenolic acid.

    abstract::Mycophenolic acid, the active metabolite of the immunosuppressant and antiproliferative agent, mycophenolate mofetil, is primarily metabolized by glucuronidation to the inactive 7-O-glucuronide. Although the uridine diphosphate (UDP) 7-O-glucuronide is the principal excretion product of this drug, carboxyl-linked gluc...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,评审


    authors: Mackenzie PI

    更新日期:2000-02-01 00:00:00

  • Liquid chromatographic determination of piroxicam in serum.

    abstract::A sensitive method for monitoring serum piroxicam (Feldene) is described. The assay requires 1.0 ml of specimen and involves chloroform extraction from an acidified mixture followed by concentration and injection into a liquid chromatograph. Column effluent is monitored at 330 nm. Retention times of piroxicam and the ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Fraser AD,Woodbury JF

    更新日期:1983-06-01 00:00:00

  • Michaelis-Menten kinetics and the steady-state serum phenytoin/hydroxyphenytoin ratio.

    abstract::The effect of nonlinear kinetics on the steady-state ratio of serum phenytoin (PHT) to total 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) was studied in epileptic patients. In each patient, the ratio increased in a nonlinear fashion in relation to both the PHT dose and the PHT serum level. Patients with longer appar...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Bourgeois BF,Wad N

    更新日期:1985-01-01 00:00:00

  • Effect of plasma exchange on flumequine pharmacokinetics: comparison with control kinetics.

    abstract::The effect of plasma exchange (PE) on the pharmacokinetics of flumequine (Apurone) was studied in eight patients receiving a single oral dose of 800 mg. The maximum concentration (38 micrograms/ml) and time to maximum concentration (2.6 h) values were not significantly altered by PE beginning 3 h after administration ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Royer-Morrot MJ,Gérard A,Zhiri A,Schooneman F,Dureux JB,Royer RJ

    更新日期:1991-07-01 00:00:00

  • Monitoring of plasma methadone: intercorrelation between immunoassay and gas chromatography-mass spectrometry.

    abstract::Determination of plasma methadone is essential in connection with dose adjustments for patients participating in methadone maintenance programs. We successfully adapted the existing fluorescence polarization immunoassay (FPIA) kit intended for urinary methadone to plasma assays. A concentration interval of 50-900 ng/m...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Beck O,Boreus LO,Borg S,Jacobsson G,Lafolie P,Stensiö M

    更新日期:1990-09-01 00:00:00

  • Urinary desipramine hydroxylation index and steady-state plasma concentrations of imipramine and desipramine.

    abstract::An index of desipramine (DMI) hydroxylation, calculated as the ratio between the amounts of DMI and 2-hydroxydesipramine (2-OH-DMI) excreted in urine after 25 mg orally, was determined in 16 depressed patients. The index varied almost 100-fold between the patients and correlated significantly to the steady-state plasm...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Spina E,Arena A,Pisani F

    更新日期:1987-06-01 00:00:00

  • Quantification of Delta9-tetrahydrocannabinol and its major metabolites in meconium by gas chromatographic-mass spectrometric assay: assay validation and preliminary results of the "meconium project".

    abstract::A rapid and simple procedure based on gas chromatography-mass spectrometry (GC-MS) is described for determination of Delta-tetrahydrocannabinol (THC), 11-hydroxy-Delta-tetrahydrocannabinol (THC-OH) and 11-nor-Delta-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in meconium using Delta-tetrahydrocannabinol (Delta-TH...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Marchei E,Pellegrini M,Pacifici R,Palmi I,Lozano J,García-Algar O,Pichini S

    更新日期:2006-10-01 00:00:00

  • Clinical relevance of therapeutic drug monitoring of digoxin and gentamicin in the saliva of children.

    abstract::Digoxin and gentamicin are widely used in pediatric medicine, and therapeutic monitoring is mandatory because of their narrow margin of safety and wide interpatient and intrapatient pharmacokinetic variabilities. Saliva sampling may be of potential interest, especially in children, in whom blood sampling is often diff...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Berkovitch M,Bistritzer T,Aladjem M,Burtin P,Dagan T,Chen-Levi Z,Freedom R,Koren G

    更新日期:1998-06-01 00:00:00

  • Evaluation of cross-reactivity of urinary digoxin-like substance in different radioimmunoassays.

    abstract::For the accuracy of routine monitoring of digoxin and digitoxin it seems important to get information on the cross-reactivity of endogenous digitalis-like substances (EDLS). To obtain EDLS, urine was passed on Sep-Pak columns and eluted in fractions by increasing concentrations of acetonitrile. Dilution series of two ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Vinge E,Ekman R

    更新日期:1988-01-01 00:00:00

  • Vancomycin Area Under the Curve Simplified.

    abstract:BACKGROUND:Serum trough concentrations as the sole means of monitoring safety and efficacy of vancomycin are insufficient. The daily area under the curve (AUC24) of serum concentration versus time to minimum inhibitory concentration (MIC) ratio of greater than 400 mg × h/L has emerged as a more robust dosing target. A ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Lewis P

    更新日期:2018-06-01 00:00:00

  • A simple method for quantifying fentanyl, sufentanil, or morphine in discard syringes from anesthesia procedures.

    abstract::Fentanyl, sufentanil, and morphine are commonly used in the conduct of anesthesia. Medical staff working with these drugs are at high risk of addiction. To detect and prevent diversion, a method was developed to quantify these drugs in discard syringes using the BioRad REMEDi HS Drug Profiling System. For fentanyl, th...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Holth LS,Friesen R,Green C,Krahn J

    更新日期:2002-10-01 00:00:00

  • Mycophenolic acid plasma concentrations: influence of comedication.

    abstract::Mycophenolate mofetil (MMF) in combination with cyclosporine (CsA) or Tacrolimus (TAC) has been show to be a potent immunosuppressive agent. The authors assessed the mycophenolic acid (MPA) plasma levels achieved in clinical practice and evaluated the effect of concomitant administration of CsA and TAC . One hundred f...

    journal_title:Therapeutic drug monitoring

    pub_type: 临床试验,杂志文章


    authors: Pou L,Brunet M,Cantarell C,Vidal E,Oppenheimer F,Monforte V,Vilardell J,Roman A,Martorell J,Capdevila L

    更新日期:2001-02-01 00:00:00

  • Low oral bioavailability and pharmacokinetics of senkyunolide a, a major bioactive component in Rhizoma Chuanxiong, in the rat.

    abstract::The pharmacokinetics of senkyunolide A, one of the major bioactive ingredients in the traditional Chinese medicinal herb Rhizoma Chuanxiong, which is commonly used for the treatment of cardiovascular diseases, was studied in rats. After intravenous (IV) administration, senkyunolide A was extensively distributed (Vd/F:...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Yan R,Lin G,Ko NL,Tam YK

    更新日期:2007-02-01 00:00:00

  • Pentobarbital quantitation using EMIT serum barbiturate assay reagents: application to monitoring of high-dose pentobarbital therapy.

    abstract::Pentobarbital serum concentrations associated with a high-dose therapeutic regimen were determined using EMIT immunoassay reagents. Replicate analyses of serum controls resulted in a within-assay coefficient of variation of 5.0% and a between-assay coefficient of variation of 10%. Regression analysis of 44 serum sampl...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Pape BE,Cary PL,Clay LC,Godolphin W

    更新日期:1983-01-01 00:00:00

  • Effects of smoking on nortriptyline plasma concentrations in depressed patients.

    abstract::The pharmacokinetic parameters of half-life, volume of distribution, and steady-state nortriptyline plasma concentration normalized to a 100-mg/day maintenance dose were calculated in nine smokers and 15 nonsmokers. The mean normalized total nortriptyline concentration for the smokers of 118 +/- 33 ng/ml was significa...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Perry PJ,Browne JL,Prince RA,Alexander B,Tsuang MT

    更新日期:1986-01-01 00:00:00

  • Quantitative determination of tolbutamide and its metabolites in human plasma and urine by high-performance liquid chromatography and UV detection.

    abstract::An isocratic, high-performance liquid chromatography method has been developed for simultaneous determination of the oral antidiabetic tolbutamide and two of its metabolites, 4-hydroxytolbutamide and carboxytolbutamide, in human plasma and urine. The method was based on simple one-step liquid-liquid extraction with te...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Hansen LL,Brøsen K

    更新日期:1999-12-01 00:00:00

  • Extended-Interval Dosing of Gentamicin Aiming for a Drug-Free Period in Neonates: A Prospective Cohort Study.

    abstract:BACKGROUND:Current gentamicin dosing algorithms in adult populations target a high peak concentration (Cmax) assuring efficacy and a drug-free period (concentration <0.5 mg/L) preventing toxicity. In contrast, gentamicin-based regimens in neonatal sepsis often aim for lower peak levels and trough concentrations of 0.5-...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: van Maarseveen EM,Sprij A,Touw DJ

    更新日期:2016-06-01 00:00:00

  • Pharmacokinetic studies of rifampicin in the elderly.

    abstract::The pharmacokinetics of rifampicin (RMP) and its principal active metabolite desacetylrifampicin (DA-RMP) were studied in six subjects, ranging in age from 78 to 95 years, after single oral doses of 10 mg/kg RMP. The maximal plasma concentrations (Cmax) and the elimination half-lives (t 1/2 beta) of RMP are 8.83 +/- 1...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Advenier C,Gobert C,Houin G,Bidet D,Richelet S,Tillement JP

    更新日期:1983-01-01 00:00:00

  • Fluconazole bioequivalence study: quantification by tandem mass spectrometry.

    abstract::To develop a new method for quantifying fluoconazole in human plasma and to compare the bioavailability of two fluconazole capsule formulations, an open, randomized, two-period crossover study with a one-week washout interval was conducted in 24 healthy volunteers. Plasma samples were obtained up to 168 hours after dr...

    journal_title:Therapeutic drug monitoring

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Moraes LA,Lerner FE,Moraes ME,Moraes MO,Corso G,De Nucci G

    更新日期:1999-04-01 00:00:00

  • The use of TDM data to assess the validity of defined daily doses of antiepileptics: a comparison between a Czech and Swedish University Hospital.

    abstract::Prescribed daily doses (PDDs) of antiepileptic drugs (AED) (N03A ATC group) were recorded for drugs used in monotherapy or in combination therapy in the University Hospitals in Ostrava, Czech Republic and Huddinge, Sweden. Plasma concentrations were used as an indicator of the quality of treatment. PDDs were compared ...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,多中心研究


    authors: Koristkova B,Sjöqvist F,Grundmann M,Bergman U

    更新日期:2006-10-01 00:00:00

  • Risperidone and Venlafaxine Metabolic Ratios Strongly Predict a CYP2D6 Poor Metabolizing Genotype.

    abstract:PURPOSE:To investigate the predictive value of the risperidone and venlafaxine metabolic ratios and CYP2D6 genotype. METHODS:The determination of risperidone, 9-hydroxyrisperidone, and venlafaxine, O-desmethylvenlafaxine, N-desmethylvenlafaxine and CYP2D6 genotype was performed in 425 and 491 patients, respectively. T...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章


    authors: Mannheimer B,Haslemo T,Lindh JD,Eliasson E,Molden E

    更新日期:2016-02-01 00:00:00

  • The role of proton pump inhibitors on early mycophenolic acid exposure in kidney transplantation: evidence from the CLEAR study.

    abstract:INTRODUCTION:Proton pump inhibitors (PPIs) are often prescribed posttransplantation to prevent gastrointestinal complications. A series of recent studies have reported a relationship between PPI comedication and decreased mycophenolic acid (MPA) exposure. The objective of this subanalysis of the CLEAR data set was to d...

    journal_title:Therapeutic drug monitoring

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Kiberd BA,Wrobel M,Dandavino R,Keown P,Gourishankar S

    更新日期:2011-02-01 00:00:00