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 = 6 per group) were orally treated with 2.5 or 5 mg/kg of mycophenolate mofetil (MMF), either alone or in combination with 5 mg/kg CsA or 4 mg/kg TRL. Blood was obtained before and at different times after dosing. For both in vitro and in vivo studies, mitogen-stimulated whole blood was analyzed by flow cytometry to determine inhibition of expression of lymphocyte proliferation (proliferating cell nuclear antigen, PCNA) and T-cell activation (eg, CD25). Plasma MPA concentrations were measured by HPLC, and whole-blood CsA and TRL concentrations were quantified using LC-MS/MS. In vitro, low concentrations of 250 and 500 nM MPA acted additively with CsA and overadditively with TRL to suppress lymphocyte function, whereas higher MPA concentrations (1000 nM) in these combinations did not further increase inhibition compared with monotherapy with CsA or TRL alone. In vivo, the MPA AUC0-24 showed a dose-dependent increase. CsA and TRL AUC0-24 were not influenced by the MMF dose. Combination therapy increased inhibition of lymphocyte function compared with MMF monotherapy with a pronounced effect on PCNA compared with CD25. Significant differences between 2.5 and 5 mg/kg MMF in the combination groups were observed at 2 or 6 hours after dosing because of the maximal inhibitory effect on PCNA and CD25 expression (P < 0.05, ANOVA). However, in combination with TRL no different effects on the inhibition of CD25 expression were found between the 2 MMF doses. These novel data indicate that measurement of pharmacodynamic parameters of lymphocyte function in whole blood may help to monitor drug combination therapy and provide a rationale for drug reduction to minimize toxicity without compromising efficacy.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Barten MJ,Shipkova M,Bartsch P,Dhein S,Streit F,Tarnok A,Armstrong VW,Mohr FW,Oellerich M,Gummert JFdoi
10.1097/01.ftd.0000146874.11480.8asubject
Has Abstractpub_date
2005-04-01 00:00:00pages
123-31issue
2eissn
0163-4356issn
1536-3694pii
00007691-200504000-00003journal_volume
27pub_type
杂志文章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 reverse-phase high-performance liquid chromatographic (HPLC) method for the measurement of lamotrigine (LTG) simultaneously with phenobarbitone (PB), phenytoin (PHT), and carbamazepine (CBZ) is described using hexobarbital as the internal standard. The method uses the chromophore at 307 nm to detect LTG in the prese...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199402000-00013
更新日期:1994-02-01 00:00:00
abstract::The purpose of the present study was to examine the effects of rifampicin on the single oral dose pharmacokinetics and pharmacodynamics of brotizolam. Thirteen healthy male volunteers received rifampicin 450 mg/day, or matched placebo, for 7 days in a double-blind randomized crossover manner. On the sixth day they rec...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,随机对照试验
doi:10.1097/01.ftd.0000200010.33430.0e
更新日期:2006-06-01 00:00:00
abstract::The pharmacokinetics of senkyunolide A, one of the major bioactive ingredients in the traditional Chinese medicinal herb Rhizoma Chuanxiong, which is commonly used for the treatment of cardiovascular diseases, was studied in rats. After intravenous (IV) administration, senkyunolide A was extensively distributed (Vd/F:...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31802c5862
更新日期:2007-02-01 00:00:00
abstract::The effect of nonlinear kinetics on the steady-state ratio of serum phenytoin (PHT) to total 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) was studied in epileptic patients. In each patient, the ratio increased in a nonlinear fashion in relation to both the PHT dose and the PHT serum level. Patients with longer appar...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198512000-00007
更新日期:1985-01-01 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::A rapid and simple procedure based on gas chromatography-mass spectrometry (GC-MS) is described for determination of Delta-tetrahydrocannabinol (THC), 11-hydroxy-Delta-tetrahydrocannabinol (THC-OH) and 11-nor-Delta-tetrahydrocannabinol-9-carboxylic acid (THC-COOH) in meconium using Delta-tetrahydrocannabinol (Delta-TH...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/01.ftd.0000245380.95186.13
更新日期:2006-10-01 00:00:00
abstract::Pentobarbital serum concentrations associated with a high-dose therapeutic regimen were determined using EMIT immunoassay reagents. Replicate analyses of serum controls resulted in a within-assay coefficient of variation of 5.0% and a between-assay coefficient of variation of 10%. Regression analysis of 44 serum sampl...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1983-01-01 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: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:PURPOSE:Substance use disorder often coexists with other psychiatric disorders, resulting in the simultaneous use of recreational and prescription drugs. The authors aimed to identify potential pharmacokinetic and pharmacodynamic interactions between new psychoactive substances of the cathinone class and specific presc...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000682
更新日期:2020-02-01 00:00:00
abstract:BACKGROUND:Stiripentol (STP) was approved as an orphan drug in 2007 in Europe as adjunctive therapy with valproic acid (VPA) and clobazam (CLB) for Dravet syndrome. Dravet syndrome is a highly pharmacoresistant form of epilepsy, which starts in early childhood. Data about STP pharmacokinetics and interactions are still...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31825dc4a6
更新日期:2012-08-01 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::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::The evaluation of a radioimmunoassay (RIA) for the monitoring of cyclosporine (CSA) that utilizes a monoclonal antibody specific for the parent compound is described. The assay exhibited good analytical recovery (greater than 95%), precision (coefficient of variation less than 10%), and linearity in plasma and whole b...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198804000-00013
更新日期:1988-01-01 00:00:00
abstract::A 64-year-old man on chronic hemodialysis for end-stage renal disease developed peritoneal carcinomatosis, and palliative chemotherapy with fluorouracil was started. The drug was administered (325 mg/m as IV bolus, at 2 PM) on 2 separate occasions, ie, 1 hour after dialysis and 2 days later, 49 hours after dialysis. T...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/01.ftd.0000183384.89275.f4
更新日期:2005-12-01 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 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::A rapid and sensitive method for the quantitation of valproic acid in tears has been developed using gas chromatography/electron capture negative chemical ionization/mass spectrometry. Valproic acid was converted directly into its pentafluorobenzyl ester derivative without the need to perform any extraction from the b...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200012000-00011
更新日期:2000-12-01 00:00:00
abstract::We describe a patient with invasive pulmonary aspergillosis on extracorporeal membrane oxygenation therapy in which therapeutic drug monitoring and individualization of therapy by measuring voriconazole plasma concentrations were performed. ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181898b0c
更新日期:2008-12-01 00:00:00
abstract::Pharmacokinetic and pharmacodynamic interactions between the gastrokinetic drug cisapride and the antipsychotic drugs bromperidol and haloperidol were studied in 29 schizophrenic inpatients. Fourteen patients were taking bromperidol (12-24 mg/d), and 15 were taking haloperidol (12-36 mg/d). Cisapride 10 mg/d was coadm...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-199906000-00007
更新日期:1999-06-01 00:00:00
abstract::The authors have developed a simple isocratic high-pressure liquid chromatographic (HPLC) assay for the simultaneous determination of lamotrigine and other frequently coadministered antiepileptic drugs in serum samples. Lamotrigine extraction was performed on a reversed-phase Oasis HBL preparation column. The eluates ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200010000-00019
更新日期:2000-10-01 00:00:00
abstract::Drugs metabolized by cytochrome CYP3A isoenzymes have wide interindividual variability and normally distributed plasma clearance distributions. This makes precise dosing difficult to achieve clinically, which may compromise safe therapy. We hypothesized that with potent inhibition of CYP3A, we could clinically render ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/01.ftd.0000194497.55269.d9
更新日期:2006-04-01 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::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 reversed-phase C-18 high-performance liquid chromatography (HPLC) assay without a prior extraction step for dihydroquinidine (HQD) in serum is described. The method is selective and useful for monitoring HQD and its presumed metabolites, quinidine (QD), N-oxide QD, 3-hydroxy QD (3-OHQD), and 10-11-d...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198412000-00017
更新日期:1984-01-01 00:00:00
abstract::The pharmacokinetic parameters of half-life, volume of distribution, and steady-state nortriptyline plasma concentration normalized to a 100-mg/day maintenance dose were calculated in nine smokers and 15 nonsmokers. The mean normalized total nortriptyline concentration for the smokers of 118 +/- 33 ng/ml was significa...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198609000-00007
更新日期:1986-01-01 00:00:00
abstract::An original, sensitive, and specific high-performance liquid chromatographic (HPLC) assay was developed for the quantitation of morphine and its two major metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G), in human plasma and cerebrospinal fluid (CSF) and in rat plasma, using hydromorphone as ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199404000-00016
更新日期:1994-04-01 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::Assessment of renal function and relating this parameter to amino-glycoside clearance is important for an appropriate individualization of dosage regimens in patients with impaired renal function. However, it has been suggested that in cystic fibrosis (CF), creatinine clearance (CrCl) is not a good predictor of tobram...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199610000-00007
更新日期:1996-10-01 00:00:00