Abstract:
:Sotrastaurin (AEB071) is an investigational immunosuppressant that blocks T-lymphocyte activation through protein kinase C inhibition. It is currently in Phase II of clinical development for the prevention of acute rejection after solid organ transplantation. In renal transplant clinical trials, sotrastaurin has been administered at doses of 200 to 300 mg twice daily. Using a validated liquid chromatography method with tandem mass spectrometry, steady-state predose blood concentrations averaged approximately 600 and 900 ng/mL at these dose levels, respectively. Sotrastaurin is primarily metabolized through CYP3A4. There is one active metabolite, N-desmethyl-sotrastaurin, that is present at low blood concentrations (less than 5% of the parent exposure). The elimination half-life of sotrastaurin averages 6 hours. Clinical drug interaction studies to date have demonstrated that sotrastaurin increases the area under the concentration-time curve of everolimus 1.2-fold and of tacrolimus twofold. Conversely, sotrastaurin area under the concentration-time curve is increased up to 1.8-fold by cyclosporine and 4.6-fold by ketoconazole. Blood samples from renal transplant patients receiving sotrastaurin were stimulated ex vivo by protein kinase C-dependent pathways. Inhibition of cytokine production, expression of CD69, and thymidine uptake served as biomarkers that demonstrated the ability of sotrastaurin to inhibit T-cell activation and proliferation at the doses used in these studies. Phase II trials have paired sotrastaurin with tacrolimus, mycophenolic acid, or everolimus. The clinical and pharmacokinetic results of these and upcoming trials will determine the optimal immunosuppressive regimen to benefit from sotrastaurin's novel mechanism of action and whether therapeutic drug monitoring will be beneficial.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Kovarik JM,Slade Adoi
10.1097/FTD.0b013e3181ee9e26subject
Has Abstractpub_date
2010-10-01 00:00:00pages
540-3issue
5eissn
0163-4356issn
1536-3694journal_volume
32pub_type
杂志文章,评审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::This study was undertaken to model the relationship between clonazepam plasma concentrations and a central nervous system adverse effect (impairment of the psychomotor performance) following the oral administration of immediate-release tablets of clonazepam in healthy volunteers. Such a (P)pharmacokinetic/(P)pharmacod...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,随机对照试验
doi:10.1097/FTD.0b013e3181b1dd76
更新日期:2009-10-01 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::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::The authors aimed to evaluate the utility of the history and clinical signs for predicting ingestion of poisons in children. A prospective cohort study was performed of all patients presenting with suspected poisoning to a pediatric emergency department over a 13-month period. Clinical data were collected on a preform...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200312000-00012
更新日期:2003-12-01 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 neurophysiologic test battery (consisting of a 24-hour, seven-channel electroencephalogram [EEG], EEG spectral analysis, multiple sleep latency test, visual evoked potentials, critical flicker fusion, and visual contrast sensitivity) was administered twice to 16 patients with juvenile myoclonic epilepsy (JME) in a d...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00007691-199902000-00014
更新日期:1999-02-01 00:00:00
abstract::Recent literature has urged caution in the interpretation of vancomycin serum concentrations in patients with end-stage renal disease (ESRD), because falsely elevated levels in excess of 70% have been reported with the most commonly used fluorescence polarization immunoassay (FPIA). The purpose of this study was to ev...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199804000-00016
更新日期:1998-04-01 00:00:00
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
doi:10.1097/00007691-200002000-00002
更新日期:2000-02-01 00:00:00
abstract:OBJECTIVE:This naturalistic therapeutic drug monitoring (TDM) study aimed to evaluate the relationship between dosage, serum concentration, and clinical outcome in children and adolescents treated with the serotonin reuptake inhibitor sertraline for different indications. METHODS:Steady-state trough serum concentratio...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31827a1aad
更新日期:2013-02-01 00:00:00
abstract::Levels of the anticonvulsant drugs phenobarbitone, phenytoin, carbamazepine, and primidone were measured in the plasma and saliva of 202 epileptic children (5 months-18 years old). Gas-liquid chromatography (GLC) and EMIT immunoassay were used to analyse the samples. Saliva to plasma ratios were as follows (means +/- ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198102000-00006
更新日期:1981-01-01 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:Valproic acid (VPA) is frequently used together with clozapine (CLZ) as mood-stabilizer or for the prevention of seizures in patients with psychotic disorders. VPA is known to reduce levels of the pharmacologically active CLZ-metabolite N-desmethylclozapine (N-DMC), but factors determining the degree of this...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000619
更新日期:2019-08-01 00:00:00
abstract::Toxicity from ingestion of the oleander plant is common. Oleandrin, the oleander glycoside, has structural similarity to cardiac glycoside digoxin and is known to cross react with various digoxin immunoassays. The authors studied the cross reactivity of oleandrin and its deglycosylated congener oleandrigenin with a fl...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199708000-00017
更新日期:1997-08-01 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::Designer drugs of the methylenedioxyphenylalkylamine type are increasingly abused. Studies on their metabolism in humans are necessary to develop a reliable gas chromatography--mass spectrometry (GC-MS) screening procedure. Such a method must allow their detection in urine for drug testing in clinical and forensic tox...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199608000-00027
更新日期:1996-08-01 00:00:00
abstract::A novel liquid chromatography-mass spectrometry (LC-MS) method was developed and validated for quantification of topiramate (TPM) and its metabolites 10-hydroxy topiramate (10-OH-TPM), 9-hydroxy topiramate (9-OH-TPM), and 4,5-O-desisopropylidene topiramate (4,5-diol-TPM) in plasma and urine. The method uses 0.5 mL of ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200306000-00012
更新日期:2003-06-01 00:00:00
abstract::Plasma clonazepam (CZP) and its metabolite [7-aminoclonazepam (7ACZP) and 7-acetamidoclonazepam (7AACZP)] concentrations were measured during a single dosing interval in 10 pediatric epilepsy patients (2-18 years, 11-102 kg) who had been receiving CZP therapeutically from 2 weeks to 4 years. These concentrations were ...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-199602000-00001
更新日期:1996-02-01 00:00:00
abstract:BACKGROUND:Human immunodeficiency virus (HIV)-infected individuals show large interindividual variation in response to antiretroviral therapy. Efavirenz (EFV) and nevirapine (NVP) are nonnucleoside reverse transcriptase inhibitors, which are prescribed in combination with other antiretroviral therapy in so-called highl...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31824868f3
更新日期:2012-04-01 00:00:00
abstract:BACKGROUND:Analysis of residual gene expression of the nuclear factor of activated T cell (NFAT)-regulated genes has been developed as a pharmacodynamic biomarker to monitor therapy with calcineurin inhibitors. The availability of commercial primer sets (Search-LC) and the well-established assay protocol makes this bio...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000340
更新日期:2016-12-01 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::Bayesian estimation (BE) of pharmacokinetic parameters enables the clinician to adjust the dosage of high-dose methotrexate (HDMTX) to correct the inter- and intraindividual variation of concentrations that are responsible for severe toxicity. In this study of 672 HDMTX infusions, we validated an approach that consist...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199510000-00007
更新日期:1995-10-01 00:00:00
abstract::Four different immunoassays were used to measure cyclosporine A (CsA) plasma (20 degrees C) levels in heart and kidney transplant recipients. Two radioimmunoassays (RIAs) (Sandimmune and Cyclotrac) and the fluorescence polarization immunoassay (FPIA) were based on polyclonal antibodies, whereas the fourth (Cyclotrac-S...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199011000-00006
更新日期:1990-11-01 00:00:00
abstract::Lamotrigine (LG), phenytoin (PY), carbamazepine (CM), and carbamazepine epoxide (CE) are measured with an optimized procedure that uses thin sorbent extraction disks and a highly selective, sterically protected bonded silica high-performance liquid chromatography (HPLC) column. Routinely, serum (200 microliters at pH ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199706000-00009
更新日期:1997-06-01 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::With the introduction of a cyclosporin monitoring strategy based on the use of a sample collected 2 hours after dosing (C2) rather than the predose sample (C0), there was concern that the differences in blood cyclosporin results from the various assay systems would result in assay-specific target ranges for C2 monitor...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/00007691-200304000-00005
更新日期:2003-04-01 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
abstract:BACKGROUND:Cyclosporine A (CsA) is used as a posttransplantation immunosuppressant drug, and careful monitoring of CsA concentration in whole blood is essential. A new automated electrochemiluminescence immunoassay (ECLIA) for CsA measurement has been assessed in a multicenter evaluation. METHODS:Residual EDTA whole b...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,多中心研究
doi:10.1097/FTD.0000000000000068
更新日期:2014-10-01 00:00:00
abstract::Their common clinical use, frequency of adverse effects, serious therapeutic indications, treatment failures, and availability of sensitive assays make corticosteroids such as prednisone and prednisolone candidates for therapeutic drug monitoring. Complicating the interpretation of plasma drug concentrations are the f...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-198004000-00011
更新日期:1980-01-01 00:00:00
abstract::The selection of an appropriate therapy and dosing regimen is a significant challenge in the treatment of cancer. Although there are recommended standardized chemotherapy protocols for some types of cancer, protocol changes that usually only occur after large clinical trials demonstrate improvements and individual pat...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000701
更新日期:2020-02-01 00:00:00