Abstract:
BACKGROUND:Cytochrome P450 3A (CYP3A) isoenzyme metabolic activity varies between individuals and is therefore a possible candidate of influence on the therapeutic outcome of the tyrosine kinase inhibitor imatinib in patients with chronic myeloid leukemia (CML). The aim of this study was to investigate the influence of CYP3A metabolic activity on the plasma concentration and outcome of imatinib in patients with CML. METHODS:Forty-three patients with CML were phenotyped for CYP3A activity using quinine as a probe drug and evaluated for clinical response parameters. Plasma concentrations of imatinib and its main metabolite, CGP74588, were determined using liquid chromatography-mass spectrometry. RESULTS:Patients with optimal response to imatinib after 12 months of therapy did not differ in CYP3A activity compared to nonoptimal responders (quinine metabolic ratio of 14.69 and 14.70, respectively; P = 0.966). Neither the imatinib plasma concentration nor the CGP74588/imatinib ratio was significantly associated with CYP3A activity. CONCLUSIONS:The CYP3A activity does not influence imatinib plasma concentrations or the therapeutic outcome. These results indicate that although imatinib is metabolized by CYP3A enzymes, this activity is not the rate-limiting step in imatinib metabolism and excretion. Future studies should focus on other pharmacokinetic processes so as to identify the major contributor to patient variability in imatinib plasma concentrations.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Skoglund K,Richter J,Olsson-Strömberg U,Bergquist J,Aluthgedara W,Ubhayasekera SJ,Vikingsson S,Svedberg A,Söderlund S,Sandstedt A,Johnsson A,Aagesen J,Alsenhed J,Hägg S,Peterson C,Lotfi K,Gréen Hdoi
10.1097/FTD.0000000000000268subject
Has Abstractpub_date
2016-04-01 00:00:00pages
230-8issue
2eissn
0163-4356issn
1536-3694journal_volume
38pub_type
杂志文章abstract:BACKGROUND:Desmopressin (D-amino D-arginine vasopressin: dDAVP) is used for the treatment of patients with hemophilia A and Von Willebrand disease. Studies on the rationale of dosing are scarce and mainly focus on the underlying causes of the vast differences in desmopressin response among individuals. The aim of this ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000791
更新日期:2020-12-01 00:00:00
abstract:BACKGROUND:No information on the pharmacokinetic characteristics of amlodipine (AML) metabolites is available. This study aimed to develop a method based on isocratic liquid chromatography coupled to tandem mass spectrometry for the simultaneous determination of AML and its 2 major metabolites, dehydroamlodipine (DH-AM...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000449
更新日期:2017-12-01 00:00:00
abstract:BACKGROUND:We report a feasibility study based on our large-scale experience with mycophenolate mofetil dose adjustment based on mycophenolic acid interdose area under the curve (AUC) in renal transplant patients. METHODS:Between 2005 and 2010, 13,930 requests for 7090 different patients (outside any clinical trial) w...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31821633a6
更新日期:2011-06-01 00:00:00
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
doi:10.1097/01.ftd.0000146874.11480.8a
更新日期:2005-04-01 00:00:00
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
doi:10.1097/FTD.0b013e31826a6306
更新日期:2012-12-01 00:00:00
abstract::The plasma binding of phenytoin and the relationship between phenytoin concentrations in salivary and plasma ultrafiltrates were evaluated in pediatric epileptic patients aged 2-15 years. Paired samples of plasma and saliva were ultrafiltered through an Amicon YMT membrane. Phenytoin concentrations were measured by a ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198309000-00014
更新日期:1983-01-01 00:00:00
abstract::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 imati...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31820beb02
更新日期:2011-04-01 00:00:00
abstract::The authors refer to their experience with alternative matrices to supervise the methadone therapy of heroin abusers. For this purpose, hair, sweat, and urine samples were collected from 10 heroin addicts and from a control group and were submitted to gas chromatographic/mass spectroscopic analysis for methadone and i...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31811f1bbe
更新日期:2007-08-01 00:00:00
abstract::Vancomycin is widely used in the prophylaxis and treatment of infections in neutropenic patients with cancer. The objective of this study was to analyze liver damage effects on vancomycin pharmacokinetics and determine the necessity for liver function evaluation when selecting vancomycin dosing schedules in these pati...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200006000-00004
更新日期:2000-06-01 00:00:00
abstract::Monitoring of serum voriconazole concentrations has been proposed to optimize therapeutic effect and minimize toxicity. However, little is known about the clinical use of voriconazole therapeutic drug monitoring (TDM) by treating physicians. Four hundred seventy-eight episodes corresponding with 161 adult patients (me...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181ea3de6
更新日期:2010-10-01 00:00:00
abstract:BACKGROUND:Thiopurine S-methyltransferase (TPMT) is an excellent example of an enzyme whose pharmacogenetic polymorphisms affect efficacy and toxicity of a drug. The association between TPMT activity and thiopurine-related myelosuppression is well recognized. To study the significance of TPMT deficiency in thiopurine m...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31826ec4b4
更新日期:2012-10-01 00:00:00
abstract:BACKGROUND:Recent studies suggest that 5-fluorouracil (5-FU) dosing by use of pharmacokinetic (PK) parameters is superior to the traditional body surface area (BSA) method in colorectal cancer therapy. The purpose of this study was to compare the estimated efficacy and toxicity of the use of PK-guided versus BSA-based ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,meta分析
doi:10.1097/FTD.0000000000000238
更新日期:2016-02-01 00:00:00
abstract::A variety of medications are used in treating patients infected with the human immunodeficiency virus (HIV). These medications are used to control viremia and to prevent and treat opportunistic infections. An individual is often required to take numerous drugs at the same time and thus clinicians are confronted with p...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-200112000-00001
更新日期:2001-12-01 00:00:00
abstract::Major advances in immunosuppression and reductions in the rates of acute rejection have led to increasing graft and patient survival rates during the past two decades. Chronic dysfunction of the renal allograft, however, remains a major clinical problem and probably represents the end result of the complex interplay b...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-200202000-00007
更新日期:2002-02-01 00:00:00
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
doi:10.1097/00007691-200102000-00007
更新日期:2001-02-01 00:00:00
abstract::Hyperlipidemia interferes with spectrophotometric assays of a number of analytes. No interference was found in the assay of gentamicin, phenytoin, or phenobarbital due to turbidity in levels of triglyceride less than or equal to 2,000 mg/dl with the Abbott TDx or Syva enzyme multiplied immunoassay (EMIT) methods. Ther...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198703000-00013
更新日期:1987-01-01 00:00:00
abstract::Studies examining associations between antidepressant response and plasma levels of bupropion and its metabolites have yielded contradictory findings. There have been no such studies in youth. This study explored such associations in 8 boys and 8 girls, age 11 to 17 years, all prescribed bupropion sustained release (S...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/01.ftd.0000197093.92559.7a
更新日期:2006-04-01 00:00:00
abstract::The purpose of this study was to construct a population pharmacokinetic (PK) metabolism (MB) model to describe ciprofloxacin (C) concentrations in plasma and vitreous and aqueous humors in 26 patients. Ciprofloxacin was given as a 3-day oral prophylactic treatment to 26 patients before vitrectomy. Plasma, vitreous, an...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-200408000-00010
更新日期:2004-08-01 00:00:00
abstract:BACKGROUND:The efficacy of drugs for the treatment of substance-related disorders is moderate at best. Therapeutic drug monitoring (TDM) could be an instrument to improve outcomes. Because TDM for most of those drugs is not established, the authors reviewed the literature and built a rating scale to detect the potentia...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/FTD.0b013e31822fbf7c
更新日期:2011-10-01 00:00:00
abstract::Rapamycin (RAPA) is a new immunosuppressive drug with a potency similar to that of FK506 and up to a 100-fold greater than that of cyclosporine (CsA). RAPA has shown to be efficacious in the prolongation of allograft survival in a number of animal models. In early studies, RAPA was administered on a dose/weight basis,...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-199312000-00004
更新日期:1993-12-01 00:00:00
abstract::The interlaboratory variability in the assay of theophylline and various anticonvulsant drugs was evaluated in a 16-month prospective study by using two independent experimental approaches: (a) a conventional method based on the distribution of quality control (QC) lyophilized human sera spiked with the test drugs (ph...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1991-03-01 00:00:00
abstract::The effects of the cytochrome P450 (CYP) 2D6 genotype and cigarette smoking on the steady-state plasma concentrations (C(ss)) of fluvoxamine (FLV) and its demethylated metabolite fluvoxamino acid (FLA) were studied in 49 Japanese depressed patients receiving FLV 200 mg/d. The C(ss) of FLV and FLA were measured by HPLC...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200308000-00008
更新日期:2003-08-01 00:00:00
abstract::The analysis of quinine in whole blood, plasma, urine, and samples dried on filter paper is described. Extraction was made with toluene followed by back-extraction into phosphate buffer. A reversed-phase liquid chromatography system with fluorescence detection was used. The within-day coefficient of variation of the m...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199308000-00012
更新日期:1993-08-01 00:00:00
abstract::A population analysis of the kinetics of lithium was performed from experimental and observational data in 113 subjects in order to propose a new approach for lithium dosage individualization. The kinetics of lithium is described by a two-compartment model. Age, body weight, height, and serum creatinine are included a...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199406000-00006
更新日期:1994-06-01 00:00:00
abstract:BACKGROUND:Anti-T lymphocyte globulin (ATLG) modulates the alloreactivity of T lymphocytes, reducing the risk of immunological posttransplant complications, in particular rejection and graft-versus-host disease, after allogeneic hematopoietic stem cell transplantation (HSCT). We developed and validated a new enzyme-lin...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000407
更新日期:2017-06-01 00:00:00
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
doi:10.1097/FTD.0b013e3181fc50d5
更新日期:2010-12-01 00:00:00
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
doi:10.1097/00007691-200106000-00008
更新日期:2001-06-01 00:00:00
abstract::Several studies suggest that therapeutic drug monitoring of protease inhibitors and nonnucleoside reverse transcriptase inhibitors may contribute to the clinical outcome of HIV-infected patients. Because of the growing number of antiretroviral drugs and of drug combinations than can be administered to these patients, ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/01.ftd.0000152680.36517.5d
更新日期:2005-04-01 00:00:00
abstract::The emerging nation of South Africa, in common with some other countries, notably Eastern Europe, is heir to decades of neglect with regards to the exposure of the majority of its population to toxic materials. In this short review, the major toxic health hazards are described. For most of these risks there are now pr...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-200202000-00027
更新日期:2002-02-01 00:00:00
abstract::The greater and more consistent absorption of cyclosporine from the microemulsion formulation (Neoral; Novartis Pharmaceuticals Ltd., Frimley, UK) when compared with that from the original form (Sandimmune; Novartis Pharmaceuticals Ltd., Frimley, UK) results in greater systemic exposure. Lung transplant recipients cou...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00007691-199902000-00004
更新日期:1999-02-01 00:00:00