Abstract:
BACKGROUND:Sirolimus is a mammalian target of rapamycin inhibitor that is being used to prevent organ rejection in kidney transplant patients often in combination with calcineurin inhibitors (CNIs; cyclosporine and tacrolimus). All 3 drugs are metabolized primarily by CYP3As. Clinical drug-drug interaction (DDI) studies of cyclosporine on sirolimus pharmacokinetics have been reported; however, there are a few clinical DDI data related to tacrolimus. METHODS:In vitro inhibition assay with sirolimus were conducted using recombinant CYP3As and human microsomes in the presence and absence of CNIs. Sirolimus concentrations were determined by validated high-performance liquid chromatography-tandem mass spectrometry (LC/MS-MS) assay. The DDI risk in terms of increase in sirolimus area under the curve (AUC) was evaluated by a mechanistic model using in vitro inhibition data and published pharmacokinetic parameters of CNIs. RESULTS:Both CNIs showed similar inhibitory effects on sirolimus metabolism in human liver and intestinal microsomes. Cyclosporine predominantly inhibited CYP3A4 (half maximal inhibitory concentration = 0.71 µM) rather than CYP3A5 (>5 µM), whereas tacrolimus showed similar inhibition for CYP3A4 (0.29 µM) and CYP3A5 (0.41 µM). The predicted increase in AUC of sirolimus during the coadministration of cyclosporine was 3.9-fold, which was comparable to the observed clinical data (3.3-fold) in healthy volunteers. Sirolimus AUC was estimated to a 2.8- to 3.2-fold increase during the coadministration of tacrolimus, based on the reported Cmax values and doses of tacrolimus in kidney transplant patients. In addition, exploratory sensitivity analysis indicated that the predicted increase in sirolimus AUC was sensitive to the free fraction of cyclosporine but not to the free fraction of tacrolimus. CONCLUSIONS:This study suggests that tacrolimus has a lower clinical DDI risk potential affecting sirolimus pharmacokinetics compared with cyclosporine in kidney transplant patients.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Emoto C,Vinks AA,Fukuda Tdoi
10.1097/FTD.0000000000000314subject
Has Abstractpub_date
2016-10-01 00:00:00pages
607-13issue
5eissn
0163-4356issn
1536-3694journal_volume
38pub_type
杂志文章abstract::Mycophenolate mofetil, the oral prodrug of mycophenolic acid, is indicated as immunosuppressive therapy after renal transplantation. To aid in the investigation of pharmacokinetic-pharmacodynamic relationships of mycophenolic acid in the clinical setting, limited blood sampling strategies have been proposed, and model...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200010000-00008
更新日期:2000-10-01 00:00:00
abstract::We presented a case of subtherapeutic linezolid concentration in a patient with bullous pemphigoid characterized by large area skin anabrosis complicated by methicillin-resistant Staphylococcus aureus infections. ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000758
更新日期:2020-08-01 00:00:00
abstract:BACKGROUND:In humans, donepezil (D) is metabolized to 5-O-desmethyl-donepezil (5DD), 6-O-desmethyl-donepezil (6DD), and donepezil-N-oxide (DNox). Although 6DD and DNox are pharmacologically active, the activity of 5DD is unknown. At present, no routine methods are available to detect D and its 3 metabolites simultaneou...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000246
更新日期:2016-02-01 00:00:00
abstract::The postulated therapeutic activity of nortriptyline metabolites has prompted investigation of dosage adjustments based on plasma levels of nortriptyline (NT) and its metabolites. The method assumes that metabolite concentrations vary independently of nortriptyline concentrations among patients. This study tests that ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198905000-00001
更新日期:1989-01-01 00:00:00
abstract::Pediatric patients with leukemia, other malignancies, and rheumatological disease receive methotrexate chronically. Because of the documented correlation between methotrexate levels of compliance and clinical outcome, it is conceivable to verify appropriate systemic exposure to the drug. Saliva sampling may be of pote...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199506000-00006
更新日期:1995-06-01 00:00:00
abstract:BACKGROUND:Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) time courses in serum and physiological and behavioral effects associated with smoking 1 or 4 "light cannabis" cigarettes were studied. Biomarkers to differentiate light cannabis versus illegal and medical cannabis use were also investigated. METHODS:Sera ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000683
更新日期:2020-02-01 00:00:00
abstract::The aims of this study were to determine the relationship between saliva and plasma methadone concentrations and the influence of variability in saliva pH. Saliva and plasma samples were taken before the daily dose of methadone in 60 patients undergoing methadone maintenance treatment (MMT). Saliva pH was measured imm...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/01.ftd.0000164392.01779.db
更新日期:2005-10-01 00:00:00
abstract::Sirolimus (rapamycin, RAPA) is a natural fermentation product (macrolide antibiotic) that has demonstrated potent immunosuppressive activity. A reverse-phase high-performance liquid chromatographic (HPLC) method is described for analysis of the drug in whole blood. The samples are purified by using liquid-liquid extra...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199702000-00022
更新日期:1997-02-01 00:00:00
abstract:BACKGROUND:Busulfan (Bu) and cyclophosphamide (Cy) are frequently included in conditioning regimens before hematopoietic stem cell transplantation (HSCT). Both drugs are detoxified by glutathione transferases (GST), and GST gene variants may explain some of the interindividual variability in pharmacokinetics and drug t...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000180
更新日期:2015-08-01 00:00:00
abstract::Nineteen acutely disturbed psychotic Asian patients were treated with a single intramuscular injection of 50 mg of zuclopenthixol acetate in Viscoleo. Patients were assessed clinically before and after treatment using the Brief Psychiatric Rating Scale (BPRS). Serum zuclopenthixol and the inactive geometric isomer tra...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199304000-00007
更新日期:1993-04-01 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::The performance of the ROCHE FP NAPA reagent, a newly reformulated monoclonal antibody-based fluorescence polarization immunoassay (FPIA) for N-acetylprocainamide, was compared with two commercially available polyclonal antibody-based immunoassays, the Abbott TDx and Syva EMIT. Although excellent correlation was obser...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199406000-00013
更新日期:1994-06-01 00:00:00
abstract::Oral posaconazole (PSZ), an azole antifungal drug, was recently introduced for the treatment of invasive fungal infections. The prescription of PSZ together with the immunosuppressant tacrolimus (TRL) was evaluated in 14 lung transplant patients with cystic fibrosis. PSZ inhibited CYP3A4 TRL metabolism, resulting in a...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31819de6fd
更新日期:2009-06-01 00:00:00
abstract::Based on the principle that vancomycin therapy requires sustained therapeutic concentrations while avoiding high peaks, some authors reported that optimal vancomycin levels could be ensured by measuring trough levels alone (Cmin). The aim of this work was to assess the performance of a one-compartment Bayesian forecas...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199712000-00002
更新日期:1997-12-01 00:00:00
abstract::Fluorescence polarization immunoassay (FPIA) (TDx, Abbott Laboratories Diagnostics, Irvin, TX, U.S.A.) is commonly utilized for quantitative determination of gentamicin serum concentrations. Recently, automated homogeneous latex agglutination (LA) (Technicon Immuno-1, Miles Diagnostics Division, Tarrytown, NY, U.S.A.)...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199408000-00010
更新日期:1994-08-01 00:00:00
abstract:BACKGROUND:There is a high coincidence between obesity and psychiatric disorders including depression. Depressive disorders are commonly treated with antidepressants, including the selective serotonin reuptake inhibitor Lexapro (escitalopram). Although candidates for elective Roux-en-Y gastric bypass (RYGB) surgery may...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000146
更新日期:2015-06-01 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::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::A simple high-performance liquid chromatography (HPLC) method for the determination of methotrexate (MTX) in biological fluids is described. The assay is rapid, the time required for analysis is less than 30 min, and it is sensitive, up to 0.01 microgram/ml, which is three times below the toxic MTX concentration. Fift...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199204000-00012
更新日期:1992-04-01 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::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::The TDx digoxin II immunoassay was used in controls and in patients not taking digoxin or any other cardiac glycoside. We report the frequency of interference thought to be caused by digoxin-like factors (DLFs). We found a high incidence of false-positive results in 15 patients with severe hepatic disease (60% false-p...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199111000-00010
更新日期:1991-11-01 00:00:00
abstract::Ergotamine has been used for therapeutic purposes since the 1950s, usually to treat vascular headache. It is highly toxic and in large, repeated doses can produce all the symptoms of ergot poisoning. A selective and sensitive method, based on liquid chromatography-tandem mass spectrometry (LC-MS2), has been developed ...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/FTD.0b013e318067dfe7
更新日期:2007-06-01 00:00:00
abstract::A minority of athletes continues to use prohibited drugs in sports to enhance performance. Athletes discovered using these drugs can be subject to severe penalties, often resulting in media and public scrutiny, especially at major events such as the Olympic Games. The International Olympic Committee (IOC) has set out ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-200002000-00022
更新日期:2000-02-01 00:00:00
abstract:BACKGROUND:Infliximab is a chimeric monoclonal antibody that binds to human tumor necrosis factor alpha and which is approved for refractory spondyloarthritis (SpA). Individual adjustment of infliximab dosage may help to improve the therapeutic response in SpA. We investigated whether a knowledge of infliximab serum co...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/FTD.0b013e318224f83d
更新日期:2011-08-01 00:00:00
abstract::A serious challenge in diagnosing fetal alcohol spectrum disorder (FASD) is the need to document alcohol use during pregnancy. Maternal/paternal alcohol abuse affects the likelihood of fetal alcohol exposure, and hence the occurrence of FASD. The objective of the current study was to document the use of the fatty acid...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31819c33b8
更新日期:2009-04-01 00:00:00
abstract::The study assessed the removal of mycophenolic acid (MPA) and its major glucuronide metabolite (MPAG) during continuous venovenous hemofiltration (CVVHF) and continuous venovenous hemodiafiltration (CVVHDF) in 4 heart transplant recipients treated for at least 6 days with mycophenolate mofetil (MMF) in addition to cyc...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181633667
更新日期:2008-02-01 00:00:00
abstract::The authors describe a case of furosemide possibly inhibiting the hypoprothrombinemic effect of warfarin. The initiation of furosemide dosing in a patient receiving a stable dose of warfarin was associated with an 28% decrease in the international normalized ration (INR). Using normal volunteers, two previous controll...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199706000-00019
更新日期:1997-06-01 00:00:00
abstract:BACKGROUND:Several factors such as low therapeutic index, large interindividual variability in systemic exposure, and the relationships between exposure and toxicity for sorafenib could justify its therapeutic drug monitoring (TDM). To support TDM, a selective and precise high-performance liquid chromatography with ult...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000027
更新日期:2014-06-01 00:00:00
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
doi:
更新日期:1990-09-01 00:00:00