Abstract:
:Metabolism of thiopurine drugs--azathioprine, 6-mercaptopurine, and 6-thioguanine--has provided a powerful pharmacogenetic model incorporating polymorphism of the enzyme thiopurine methyltransferase (TPMT) and the primary active metabolite, thioguanine nucleotide (TGN). However, a sense of uncertainty about the usefulness of TGNs and other thiopurine metabolites has appeared. This review critically appraises the basis of thiopurine metabolism and reveals the problems and complexities in TGN research. Erythrocyte TGN is used in transplantation medicine and in chronic inflammatory conditions such as Crohn's disease, as a "surrogate" pharmacokinetic parameter for TGN in the target cells: leukocytes or bone marrow. It is not generally appreciated that erythrocytes do not express the enzyme IMP dehydrogenase and cannot convert mercaptopurine to TGN, which explains some of the confusion in interpretation of erythrocyte TGN measurements. TGN routinely measured in erythrocytes derives from hepatic metabolism. Another concern is that TGN are not generally assayed directly: most methods assay the thiopurine bases. Ion-exchange HPLC and enzymatic conversion of TGNs to nucleosides have been used to overcome this, and may reveal undisclosed roles for an unusual cytotoxic nucleotide, thio-inosine triphosphate, and methylated thiopurines. There appear to be additional interactions between xanthine oxidase and TPMT, and folate and TPMT, that could predict leukopenia. Difficult questions remain to be answered, which may be assisted by technological advances. Prospective TGN studies, long overdue, are at last revealing clearer results.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Duley JA,Florin THdoi
10.1097/01.ftd.0000169061.52715.3esubject
Has Abstractpub_date
2005-10-01 00:00:00pages
647-54issue
5eissn
0163-4356issn
1536-3694pii
00007691-200510000-00018journal_volume
27pub_type
杂志文章,评审abstract::The authors describe a reverse-phase high-performance liquid chromatography-electrospray-tandem mass spectrometry method for the measurement of nicotine in human plasma. Samples (500 microL) with added deuterium-labeled d3-nicotine as an internal standard (IS) were treated with a 2-step process of ether extraction (6 ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200410000-00015
更新日期:2004-10-01 00:00:00
abstract::The interaction between valproic acid (VPA) and phenytoin (DPH) was examined during therapeutic monitoring in an epileptic outpatient population. Gas-liquid chromatographic methods were used to measure DPH and VPA concentrations. (1) In 12 patients on stable DPH regimens, the mean DPH level declined from 19.7 to 15.3 ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-197901020-00005
更新日期:1979-01-01 00:00:00
abstract::The diurnal fluctuations in free and total plasma levels of carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZ-E) and their relationship with intermittent side effects were examined in 10 epileptic patients stabilized on chronic CBZ therapy alone or in combination with phenobarbital (PB). With a t.i.d. or q.i.d....
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198412000-00005
更新日期:1984-01-01 00:00:00
abstract::The relationship between changes in cyclosporin (CyA) dose or CyA blood concentration and the reciprocal creatinine concentration was investigated by cross-correlation analysis over the first 3 postoperative months in 32 consecutive heart and heart-lung recipients. Exploratory analysis suggested that early changes in ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199208000-00003
更新日期:1992-08-01 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::Several lipophilic, cytotoxic drugs, or both, (including anticancer drugs [Vinca alkaloids, doxorubicin, cyclosporin A, and digoxin]) have proven to be actively effluxed by P-glycoprotein (P-gp) expressed at the luminal membrane of the brain capillary endothelial cells, resulting in the very low apparent blood-brain b...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-199810000-00024
更新日期:1998-10-01 00:00:00
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
doi:10.1097/FTD.0000000000000542
更新日期:2018-10-01 00:00:00
abstract:BACKGROUND:The combination of trimethoprim (TMP) and sulfamethoxazole (SMX) is used to treat a number of bacterial infections. TMP/SMX concentrations in serum are conventionally monitored using high-performance liquid chromatography (HPLC) or liquid chromatography tandem mass spectrometry. These methods require laborio...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000785
更新日期:2020-10-01 00:00:00
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...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3182804c9b
更新日期:2013-04-01 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::Pharmacokinetics of intravenous and oral pulsed high-dose dexamethasone were studied in four patients with pemphigus vulgaris. Doses for dexamethasone were varied from 100 to 300 mg. Serum concentrations were measured by high-performance liquid chromatographic procedure with diode assay detection. Bioavailability was ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199910000-00007
更新日期:1999-10-01 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::A rapid and reliable micro procedure for the high pressure liquid chromatographic analysis of cimetidine. N"-cyano-N-methyl-N'-[2-[[(5-methyl-1H-imidazol-4-yl)methyl]thio]ethyl]guanidine, in serum or plasma is described. The percentage analytical recovery of cimetidine and internal standard (beta-hydroxypropyl-theophy...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-197901030-00010
更新日期:1979-01-01 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::Steady-state serum concentrations of quetiapine were recorded in 62 psychiatric patients under routine conditions. Doses were administered twice daily, and serum quetiapine levels were measured in the morning about 12 hours after the last dose. Eight patients were in monotherapy, whereas the rest received various addi...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-200410000-00005
更新日期:2004-10-01 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::The high incidence of psychiatric illness in the postpartum period and the increasing percentage of women who breastfeed has focused attention on the treatment of breastfeeding women with psychotropic medications and, additionally, the exposure of nursing infants to these medications. Consequently, there has been an i...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200402000-00011
更新日期:2004-02-01 00:00:00
abstract::A simple and rapid liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method for the analysis of voriconazole has been developed. For comparison, serum voriconazole was measured using HPLC and bioassay. For the HPLC-MS/MS assay, samples were prepared in a deep-well block by adding 10 microL of serum to 40 mic...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200412000-00011
更新日期:2004-12-01 00:00:00
abstract::An isocratic, high-performance liquid chromatography method has been developed for simultaneous determination of the tricyclic antidepressant clomipramine and six metabolites: desmethylclomipramine, 2- and 8-hydroxy-clomipramine, 2- and 8-hydroxydesmethylclomipramine and didesmethyl-clomipramine in plasma and urine. I...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199304000-00010
更新日期:1993-04-01 00:00:00
abstract::Lidocaine is widely used in antiarrhythmic therapy, and the need to monitor the drug concentration in the blood of patients receiving lidocaine is well established. We have developed a new assay for lidocaine designed for the routine clinical therapeutic drug monitoring laboratory. A 100-microliter aliquot of blood pl...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198102000-00010
更新日期:1981-01-01 00:00:00
abstract:BACKGROUND:Non-vitamin K antagonist oral anticoagulants (NOACs) are approved for several indications for prophylaxis of thromboembolism at fixed oral doses. The analysis of NOAC activity/concentration may be required in special patient populations. Heptest coagulation assay determines both factor Xa and thrombin inhibi...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000157
更新日期:2015-06-01 00:00:00
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
doi:10.1097/00007691-200312000-00002
更新日期:2003-12-01 00:00:00
abstract::Caffeine is a potentially useful alternative to theophylline for the treatment and prevention of apnea of prematurity because of its lower toxicity and longer terminal half-life. Monitoring of salivary caffeine concentrations is less invasive than blood sampling, especially in very sick premature neonates. Caffeine ci...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00007691-199606000-00012
更新日期:1996-06-01 00:00:00
abstract::Palivizumab is a humanized, monoclonal antibody used to protect at-risk infants against respiratory syncytial virus (RSV) infection. The regular dosage scheme causes a low initial trough level and accumulation of the antibody after subsequent injections. Using a simple pharmacokinetic model, the authors devised an alt...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200206000-00020
更新日期:2002-06-01 00:00:00
abstract:BACKGROUND:Buprenorphine is currently under investigation as a pharmacotherapy to treat pregnant women for opioid dependence. This research evaluates buprenorphine (BUP), norbuprenophine (NBUP), buprenorphine-glucuronide (BUP-Gluc), and norbuprenorphine-glucuronide (NBUP-Gluc) pharmacokinetics after high-dose (14-20 mg...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,随机对照试验
doi:10.1097/FTD.0b013e318228bb2a
更新日期:2011-10-01 00:00:00
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
doi:10.1097/00007691-198706000-00001
更新日期:1987-06-01 00:00:00
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
doi:
更新日期:1994-12-01 00:00:00
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
doi:10.1097/FTD.0b013e318206a1b1
更新日期:2011-02-01 00:00:00
abstract::During once-daily dosing regimens of aminoglycosides, administration of large single doses results in high peak levels and low 24-h trough levels. However, commercial assays for monitoring aminoglycoside levels are designed to cover the smaller range of serum concentrations usually observed during multiple daily dosin...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/00007691-199504000-00005
更新日期:1995-04-01 00:00:00
abstract::Calculated creatinine clearance (CrCL) estimates are frequently used as estimates of aminoglycoside clearance (AGCL), despite being inadequately studied. Thirty surgical intensive care unit (SICU) patients with stable serum creatinines (0.6-6.3 mg/dl) and steady-state aminoglycoside levels were studied. A one-compartm...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198903000-00006
更新日期:1989-01-01 00:00:00