Abstract:
:Mixed-effect modeling has been suggested as a possible tool to detect and describe drug interactions in patient populations receiving drug combinations for the treatment of disease states. The mixed-effect modeling program, NONMEM, was used to measure the effects of the well-known digoxin-quinidine and digoxin-verapamil drug interactions in 294 patients receiving oral digoxin as hospital inpatients. Fourteen percent of the population took either quinidine or verapamil concurrently with digoxin (mean quinidine dose = 857 +/- 397 mg/day, verapamil = 261 +/- 110 mg/day). Two regression models for digoxin oral clearance were used. Model 1 used the knowledge that digoxin is eliminated by both renal and nonrenal routes (TVCL = ClNR+m.CrCl, where TVCL is the population digoxin oral clearance, ClNR is the nonrenal clearance, and m is the slope of the line that relates creatinine clearance (CrCl) to digoxin clearance); model 2 used a more conventional regression approach with a simple series of multipliers. For both models, quinidine administration decreased population digoxin oral clearance by approximately 45% and verapamil therapy decreased population digoxin oral clearance by approximately 30%. These values are similar to those found by traditional drug interaction studies conducted in small patient or normal subject populations. Mixed-effect modeling can detect clinically relevant drug interactions and produce information similar to that found in traditional pharmacokinetic crossover study designs.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Bauer LA,Horn JR,Pettit Hdoi
10.1097/00007691-199602000-00008subject
Has Abstractpub_date
1996-02-01 00:00:00pages
46-52issue
1eissn
0163-4356issn
1536-3694journal_volume
18pub_type
临床试验,杂志文章abstract::Linezolid is an antibiotic used to treat infections caused by drug-resistant gram-positive organisms, including vancomycin-resistant Enterococcus faecium, multi-drug resistant Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus. The adverse effects of linezolid can include thrombocytopenia and ne...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000710
更新日期:2020-02-01 00:00:00
abstract::Eight commercial digoxin immunoassay methods were tested in 17 subjects taking spironolactone (but not digoxin) to evaluate cross-reactivity from parent drug and/or metabolites. Four of these methods showed significant (up to 1.9 nmol/L) and variable "apparent digoxin" concentrations, despite the absence of digoxin in...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198706000-00014
更新日期:1987-06-01 00:00:00
abstract::Several studies have reported that the cytochrome P450 (CYP) 2D6 plays an important role in the fluvoxamine metabolism. However, some other studies have reported that the CYP2D6 genotype has no major impact on the fluvoxamine concentration. This study investigated the dose-dependent effect of CYP2D6-variant alleles on...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31818d73b3
更新日期:2008-12-01 00:00:00
abstract::A high-performance liquid chromatography (HPLC) method was developed for the simultaneous analysis of trimethoprim (TMP), sulphamethoxazole (SMX), and acetylsulphamethoxazole (AcSMX) in small amounts of blood. The method involved precipitation with 50 microL trichloracetic acid (1M) to 125 microL plasma or serum sampl...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00007691-199912000-00005
更新日期:1999-12-01 00:00:00
abstract::The current article describes a new assay to measure thiopurine methyltransferase (TPMT) activity from red blood cells. This method is based on the measurement of the reaction product 6-methylmercaptopurine (6-MMP) by high-performance liquid chromatography (HPLC). 6-MMP is extracted by ethyl acetate with recoveries of...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200110000-00007
更新日期:2001-10-01 00:00:00
abstract::Urinary excretion of lipocalin-type prostaglandin D synthase (L-PGDS) has been suggested to be a useful biomarker of early diabetic nephropathy. We studied whether L-PGDS is also a marker of gentamicin (GM)-induced renal damage in the "creatinine-blind" range. A prospective study was conducted in 6 patients who were g...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31819566f1
更新日期:2009-02-01 00:00:00
abstract::The analysis of pentamidine in whole blood, plasma, and urine by liquid chromatography is described. Extraction was made with a mixture of acetonitrile and chloroform followed by back-extraction into phosphate buffer. A reversed-phase chromatographic system with fluorescence detection was used. The precision of the me...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199007000-00011
更新日期:1990-07-01 00:00:00
abstract::Amprenavir is an HIV-1 protease inhibitor with high protein binding (90%) in human plasma. This study was designed to develop an assay to measure the concentration of unbound amprenavir, to study variation with time in patients, and to investigate whether ritonavir and lopinavir, other protease inhibitors that could b...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/01.ftd.0000188018.26680.98
更新日期:2006-02-01 00:00:00
abstract::Whole blood steady-state trough concentrations of cyclosporine were measured by radioimmunoassay (RIA) and TDx assays employing monoclonal antibodies in 82 samples from 39 renal transplant patients. Intra- and interassay coefficients of variation for the new TDx technique averaged 3.2 and 5.4%, respectively. In the co...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199109000-00012
更新日期:1991-09-01 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::This study examined whether salivary nicotine concentrations would provide a useful index of plasma concentrations in studies of the effects of transdermal nicotine administration. Twenty-four subject smokers abstained from smoking for 12 h prior to admission to a clinical research unit ward and for 36 h while remaini...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00007691-199310000-00012
更新日期:1993-10-01 00:00:00
abstract::The remarkably strong formation of the mycophenolic acid molecular ion from mycophenolic acid glucuronide during electrospray atmospheric pressure ionization in patients' serum samples is described. It is concluded that because of this effect appropriate chromatographic separation prior to tandem-mass spectrometric an...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200112000-00021
更新日期:2001-12-01 00:00:00
abstract::Drug discovery programs are actively exploring for therapeutic agents targeting enzymes and receptors regulating sphingolipid metabolism and biologic functions. FTY720 is a close structural analogue of sphingosine with immunomodulatory properties. After oral administration, FTY720 is phosphorylated by sphingosine kina...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-200412000-00001
更新日期:2004-12-01 00:00:00
abstract::Plasma concentrations of isepamicin, a new aminoglycoside antibiotic, were determined by radioimmunoassay (RIA), microbiological assay (MA), and high-performance liquid chromatography (HPLC) in healthy volunteers after administration of 7.5 mg/kg intramuscular dosages once daily for 10 days. Plasma samples were collec...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199712000-00012
更新日期:1997-12-01 00:00:00
abstract::It has been reported in scientific data that fluorescence polarization immunoassay (FPIA) results in overestimation of vancomycin in patients with renal failure. This overestimation is caused by interference of the degradation product, CDP-1, in this assay. Increases in vancomycin levels have also been reported in pat...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200108000-00020
更新日期:2001-08-01 00:00:00
abstract::In a crossover study balanced for sex, treatments, and treatment order, we have investigated the pharmacokinetics of diltiazem after single oral doses in 10 healthy middle-aged volunteers. The diltiazem doses employed were 60 mg and 120 mg and contained 1.85 MBq [14C] diltiazem. The absorption was rapid and did not di...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1989-09-01 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: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::An analytical technique using liquid chromatography (LC) coupled with electrospray-mass spectrometry (ESI--MS) has been developed for the simultaneous determination of five protease inhibitors (PIs): saquinavir, indinavir, ritonavir, nelfinavir, and amprenavir; and three non-nucleoside reverse transcriptase inhibitors...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200108000-00010
更新日期:2001-08-01 00:00:00
abstract::The current standard of monitoring transplant patients by drug levels is not optimal because it does not take into account the different and individual effects of immunosuppressive drugs on each patient. In this study, the authors tested immune function assays for monitoring transplant patients. Blood was collected fr...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200302000-00003
更新日期:2003-02-01 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::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::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:Recent studies suggest that 5-fluorouracil (5-FU) dosing by use of pharmacokinetic (PK) parameters is superior to the traditional body surface area (BSA) method in colorectal cancer therapy. The purpose of this study was to compare the estimated efficacy and toxicity of the use of PK-guided versus BSA-based ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,meta分析
doi:10.1097/FTD.0000000000000238
更新日期:2016-02-01 00:00:00
abstract::Effects of carbamazepine coadministration on plasma concentrations of trazodone and its active metabolite, m-chlorophenylpiperazine (m-CPP) were studied in six depressed patients treated with trazodone. The daily dose of trazodone was 150 mg in three cases and 300 mg in three cases. Carbamazepine, 400 mg/day, was coad...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199604000-00010
更新日期:1996-04-01 00:00:00
abstract::Since therapeutic drug monitoring is rapidly becoming a widely used tool in clinical medicine, we prospectively assessed 390 serum drug assays over a 4-week period to determine the appropriateness of serum sample collection. The results of appropriately collected samples were used to evaluate the ability of the physic...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198309000-00002
更新日期:1983-01-01 00:00:00
abstract::Mycophenolate mofetil (MMF) is increasingly used for the treatment of autoimmune diseases (AID). In renal transplant recipients, it has been demonstrated that adjustment of the MMF dose according to the area under the plasma concentration versus time curve (AUC) of mycophenolic acid (MPA), the active moiety of MMF, im...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181a23f1a
更新日期:2009-06-01 00:00:00
abstract::The effects of the cytochrome P450 (CYP) 2D6 genotype and cigarette smoking on the steady-state plasma concentrations (C(ss)) of fluvoxamine (FLV) and its demethylated metabolite fluvoxamino acid (FLA) were studied in 49 Japanese depressed patients receiving FLV 200 mg/d. The C(ss) of FLV and FLA were measured by HPLC...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200308000-00008
更新日期:2003-08-01 00:00:00
abstract::The ring sulfoxidation of thioridazine (THD), a widely used neuroleptic agent, yields two diastereoisomeric pairs, fast- and slow-eluting (FE and SE) thioridazine 5-sulfoxide (THD 5-SO). Until now, studies in which concentrations of these metabolites were measured in THD-treated patients have revealed no significant d...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1991-07-01 00:00:00
abstract::Monitoring of serum voriconazole concentrations has been proposed to optimize therapeutic effect and minimize toxicity. However, little is known about the clinical use of voriconazole therapeutic drug monitoring (TDM) by treating physicians. Four hundred seventy-eight episodes corresponding with 161 adult patients (me...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181ea3de6
更新日期:2010-10-01 00:00:00