Abstract:
BACKGROUND:Drug blood levels can only serve as a surrogate because of the lack of information on the drug's direct pharmacological effects in the individual patient. Measurement of the mammalian target of rapamycin (mTOR) activity dependent on the phosphorylation status of p70 S6 kinase (p70 S6K) offers a practical way for monitoring pharmacodynamic drug activity, with the potential to better assess the state of immunosuppression in individual patients. MATERIAL AND METHODS:Here, we established a novel in vitro model system by treating Jurkat cells and peripheral blood mononuclear cells with different concentrations of sirolimus after stimulation with phorbol 12-myristate 13-acetate. RESULTS:A dose-dependent reduction of the p70 S6K phosphorylation status was demonstrated by Western blot and a newly established enzyme-linked immunosorbent assay (ELISA). Relative phospho-p70 S6K values from ELISA and relative densities from Western blot analysis in peripheral blood mononuclear cells revealed a strong correlation (Spearman correlation coefficient r s = 0.7, P = 0.01). Finally, parallel assays confirmed a sirolimus dose-dependent reduction of cytokine production and cell proliferation in the in vitro model. CONCLUSIONS:Pharmacodynamic monitoring of mTOR inhibition with a p70 S6K ELISA could guide mTOR inhibitor immunosuppression therapy toward a more individualized therapy. The usage of this technique now has to be evaluated in a clinical series of patients.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Hartmann B,He X,Keller F,Fischereder M,Guba M,Schmid Hdoi
10.1097/FTD.0b013e3182804c9bsubject
Has Abstractpub_date
2013-04-01 00:00:00pages
233-9issue
2eissn
0163-4356issn
1536-3694pii
00007691-201304000-00013journal_volume
35pub_type
杂志文章abstract::The placental and milk transfer of chloroquine was studied in seven subjects and six subjects, respectively. Seven pregnant women at term were administered chloroquine phosphate (5 mg/kg) i.m. The maternal blood and arterial and venous umbilical cord blood were obtained during delivery. The maternal chloroquine blood ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198802000-00004
更新日期:1988-01-01 00:00:00
abstract::Aminoglycosides have rightly remained a cost-effective anti-microbial strategy for the treatment of gram-positive infections for some 25 years. However, in recent years there has been a review of the traditional thrice-daily administration regimen in favor of an extended dosing interval strategy that takes into accoun...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-199908000-00001
更新日期:1999-08-01 00:00:00
abstract::The aim of this study was to investigate the use of psychotropic medication and therapeutic drug monitoring in a high-security psychiatric unit and to compare the doses and serum concentrations both with the recommended intervals and with the doses and serum concentrations in a control group. One hundred thirty-two pa...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31818622c4
更新日期:2008-10-01 00:00:00
abstract::The role of drug assays for screening, diagnosis, and guiding treatment decisions in overdose patients remains unclear. The use of drug concentration data in clinical toxicology research is more problematic, with studies using drug concentrations to simply confirm ingestion in observational studies or others report dr...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181dca280
更新日期:2010-06-01 00:00:00
abstract::The emergence of point-of-care assays enabling bedside testing such as the VerifyNow P2Y12 system might prove useful in clinical settings. The aim of this study was to evaluate the ability of the VerifyNow P2Y12 assay to estimate the inhibition of platelet aggregation provided by clopidogrel in the absence of baseline...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,随机对照试验
doi:10.1097/FTD.0b013e3181757c59
更新日期:2008-06-01 00:00:00
abstract::Determination of serum concentrations of certain drugs is becoming increasingly important for optimal patient care. These drugs include many antibiotics, several antiarrhythmics, cardiac glycosides, lithium, phenytoin, some other anticonvulsants, salicylates, and theophylline. Serum level determinations can also be us...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:
更新日期:1981-01-01 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:Theophylline, a xanthine derivative drug, is used for the treatment of respiratory diseases, such as asthma, and is primarily eliminated by hepatic metabolism. There is marked interindividual variability in theophylline clearance. Therefore, the aim of this study was to evaluate the influence of chronic hepa...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000787
更新日期:2020-12-01 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::This laboratory has developed a simple and efficient solid-phase extraction method that is combined with a high-performance liquid chromatographic method for rapid and precise therapeutic monitoring of haloperidol (Haldol) blood levels. The solid-phase extraction utilizes a mixed bed column. Sensitivity of the chromat...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199410000-00011
更新日期:1994-10-01 00:00:00
abstract::Epilepsy is characterized by seizures recurring at interindividually differing time intervals. It may be difficult to assess drug response if time intervals between seizures are long. Thus, the existence of surrogate parameters that could be used to reliably identify drug efficacy and tolerability at an early stage an...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/FTD.0000000000000623
更新日期:2019-04-01 00:00:00
abstract::For the evaluation and interpretation of pharmacokinetic data reliable quantitative determinations are a requirement that can only be met by well-characterized and fully validated analytical methods. To cope with these requirements a method is being established that is based on an integrated and automated fiber-optic ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199608000-00017
更新日期:1996-08-01 00:00:00
abstract::Since the late 90s, biopharmaceuticals targeting tumor necrosis factor alpha have revolutionized the treatment of moderately to severely active inflammatory bowel disease. The robust efficacy witnessed in many patients stands in stark contrast with the observation of a proportion of patients who fail to respond or who...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/FTD.0000000000000394
更新日期:2017-08-01 00:00:00
abstract::Monoclonal antibodies (mAbs) may be used as biopharmaceuticals to treat various diseases, ranging from oncology to inflammatory and cardiovascular affections. Trustworthy analytical methods are necessary to study their pharmacokinetics, both during their development and in post-marketing studies. Because biopharmaceut...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/FTD.0000000000000419
更新日期:2017-08-01 00:00:00
abstract:UNLABELLED:Oral fluid is an attractive alternative matrix for drug testing with a noninvasive and directly observed collection, but there are few controlled cocaine administration studies to guide interpretation. MATERIALS AND METHODS:While residing on a closed research unit for up to 10 weeks under constant medical s...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181f2b729
更新日期:2010-10-01 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::Ultrafiltration techniques for the separation of bound and free ligand are dependent on minimal amounts of protein-bound drug leakage through the membrane devices. A dye-impregnated test strip protein assay (Chemstrip-9) provides a rapid, visual assessment of membrane protein leakage. The test strips are sensitive to ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198507030-00014
更新日期:1985-01-01 00:00:00
abstract::Phenytoin is an effective anticonvulsant, but high serum phenytoin concentrations may be associated with serious toxicity. The upper limit for the therapeutic serum concentration of phenytoin is considered to be 80 micromol/L. However, in some situations higher serum concentrations are needed to control seizures. The ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200206000-00010
更新日期:2002-06-01 00:00:00
abstract:INTRODUCTION:Enoxaparin is an anticoagulant used in the treatment of thromboembolic diseases. It is a hydrophilic molecule that is, predominantly, eliminated renally with few data to support dosing for subjects with renal impairment and/or obesity. A recently conducted randomized controlled clinical trial compared indi...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,随机对照试验
doi:10.1097/FTD.0b013e3181e64846
更新日期:2010-08-01 00:00:00
abstract::Thiopurine methyltransferase (TPMT) is a cytoplasmic enzyme that preferentially catalyzes the S-methylation of aromatic and heterocyclic sulphydryl compounds, such as the thiopurine drugs azathioprine, mercaptopurine, and thioguanine. These drugs form the same terminal metabolites, the thioguanine nucleotides (TGNs). ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-199810000-00014
更新日期:1998-10-01 00:00:00
abstract::After observing the phenomenon clinically, seven post-hemodialysis patients were studied for a rebound effect of gentamicin levels. Serum gentamicin levels were obtained immediately after dialysis and 1 hr postdialysis. An average 25.7% rebound occurred in the serum levels. A slow redistribution of gentamicin out of t...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198204000-00015
更新日期:1982-01-01 00:00:00
abstract::Most recent cyclosporine (CsA) pharmacokinetic (PK) studies have focused on noncompartmental analysis. Because CsA undergoes significant first-pass elimination after oral dosing, the most appropriate compartment model may need to take this process into account for the construction of a valid population PK model for Sa...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199804000-00006
更新日期:1998-04-01 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:BACKGROUND:A fast and easy-to-use liquid chromatography-tandem mass spectrometry method for the determination and quantification of 6 triazoles [fluconazole (FLZ), isavuconazole (ISZ), itraconazole (ITZ), hydroxy-itraconazole (OH-ITZ), posaconazole (PSZ), and voriconazole (VRZ)] in human plasma and serum was developed ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000438
更新日期:2017-10-01 00:00:00
abstract::Sirolimus is a new immunosuppressive drug that has been evaluated in animal experiments. The current study was conducted on humans with reformulated sirolimus in doses from 3 mg/m2 to 15 mg/m2. Sixteen renal transplant recipients were included in this phase I study to determine the safety, tolerance, and preliminary p...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00007691-199708000-00007
更新日期:1997-08-01 00:00:00
abstract::Exposure to mycophenolic acid (MPA) is highly variable among patients on standard dose mycophenolate mofetil (MMF) therapy. In addition, MPA exposure increases with time posttransplant and exposure is predictive for the development of acute rejection. Consequently, therapeutic drug monitoring (TDM) of MPA may improve ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/01.ftd.0000194504.62892.b2
更新日期:2006-02-01 00:00:00
abstract::Euthyroid women experience dramatic changes in their thyroid physiology in order to accommodate the presence of placental and fetal tissues. These adaptations to the pregnant state make it crucial to develop reliable trimester-specific intervals for thyroid parameters. Use of non-pregnant reference intervals could lea...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/01.ftd.0000211834.41844.82
更新日期:2006-06-01 00:00:00
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
doi:10.1097/FTD.0b013e3181d5eeee
更新日期:2010-08-01 00:00:00
abstract::The major goal of immunosuppressive development is improved selectivity of the drug's inhibitory action against T and B cell-mediated as opposed to nonspecific granulocyte-, monocyte-, and macrophage-mediated resistance. This enterprise demands increased knowledge of alloantigen-induced stimulation, signal transductio...
journal_title:Therapeutic drug monitoring
pub_type: 历史文章,杂志文章
doi:10.1097/00007691-199512000-00002
更新日期:1995-12-01 00:00:00
abstract::The practice of enhancing athletic performance through foreign substances was known from the earliest Olympic games. In 1967, the International Olympic Committee (IOC) established a Medical Commission responsible for developing a list of prohibited substances and methods. Drug tests were first introduced at the Olympi...
journal_title:Therapeutic drug monitoring
pub_type: 历史文章,杂志文章
doi:10.1097/00007691-200404000-00015
更新日期:2004-04-01 00:00:00