Abstract:
BACKGROUND:Posaconazole is an azole antifungal agent with a broad spectrum of activity and a manageable side-effect profile. Although the pharmacokinetics of posaconazole have been described in healthy volunteers who received the drug by means of a nasogastric tube or with nutritional supplements, the pharmacokinetics of posaconazole have not been reported in critically ill patients. METHODS:Twenty-seven patients in the general intensive care unit managed according to standard protocols were randomly allocated to dose regimens of either 400 mg twice daily or 200 mg 4 times daily. Plasma samples were collected for pharmacokinetic analysis after the first dose and at steady-state. Posaconazole plasma concentrations were compared with suggested effect targets for prophylaxis and treatment. RESULTS:Mean Cmin steady-state plasma concentrations of posaconazole were low for both regimens (306 and 137 ng/mL for 400 mg twice daily and 200 mg 4 times daily regimens, respectively), as was total exposure to posaconazole in each group [area under the concentration-time curve (AUC0-t) for first dose: 761 and 299 μg·h/L]. Only 17% of patients achieved steady-state Cmin posaconazole plasma concentrations above the suggested target for prophylaxis, and only one patient had a Cmin posaconazole concentration that exceeded the suggested target for treatment effect. Systemic exposure to posaconazole seemed to be subtherapeutic in most patients in this cohort. Poor absorption of posaconazole due to drug interactions may explain the low systemic exposure; however, further investigation is necessary. CONCLUSIONS:These data suggest that there is a need for an intraveneous formulation of the drug if it is to be used effectively in critically ill patients, and therapeutic drug monitoring is an essential tool in this setting to identify patients with low systemic exposure to prevent therapeutic failure.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Ray J,Campbell L,Rudham S,Nguyen Q,Marriott Ddoi
10.1097/FTD.0b013e31821fb197subject
Has Abstractpub_date
2011-08-01 00:00:00pages
387-92issue
4eissn
0163-4356issn
1536-3694journal_volume
33pub_type
杂志文章,随机对照试验abstract::A variety of medications are used in treating patients infected with the human immunodeficiency virus (HIV). These medications are used to control viremia and to prevent and treat opportunistic infections. An individual is often required to take numerous drugs at the same time and thus clinicians are confronted with p...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-200112000-00001
更新日期:2001-12-01 00:00:00
abstract::Indomethacin (INDO) pharmacokinetics were examined in 18 neonates on 19 occasions, before and after patent ductus arteriosus (PDA) closure. Patients received INDO as an initial dose of 0.25 mg/kg intravenously, and INDO serum concentrations were measured 2 and 8 h after the dose. Subsequent doses were individualized b...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::In 12 institutionalized epilepsy patients who had been treated 19 months (SD +/- 5) with valproic acid, 27.0 mg/kg (SD +/- 11.9), phenytoin, 6.33 mg/kg (SD +/- 1.36), and co-anticonvulsants, the mean percentage of daily free valproic acid was 11.72 (SD +/- 2.10) and of phenytoin 20.39 (SD +/- 3.32). By serial within-d...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198103000-00013
更新日期:1981-01-01 00:00:00
abstract::A method for the quantitative determination of the tricyclic antidepressant drug amitriptyline (AT) and its active major metabolite, nortriptyline (NT), in plasma is described. The method involves a three-step extraction procedure, no derivatization, and a rapid run on a gas--liquid chromatograph equipped with a nitro...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198212000-00006
更新日期:1982-01-01 00:00:00
abstract::Characterization of antibiotic pharmacokinetics in patients with renal insufficiency may be complicated by interfering substances within the assay. We compared three different assays for teicoplanin in serum and dialysate of 10 hemodialysis and six continuous ambulatory peritoneal dialysis (CAPD) patients. The microbi...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1991-11-01 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::Three automated immunoassays for digoxin in serum were evaluated--Abbott TDxII, Baxter Stratus, and Behring OPUS. The accuracy and precision of the assays were assessed by weighed-in controls and an external quality control program. Coefficients of variation of all methods in serum were < or = 10% at weighed-in concen...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199502000-00011
更新日期:1995-02-01 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 computer-based approach for estimating pharmacokinetic data and predicting plasma drug concentrations based on two measurements of plasma drug concentrations was compared with a standard two-point method for estimating aminoglycoside (AG) pharmacokinetic parameters. The computer-based technique was also used to pred...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198507030-00003
更新日期:1985-01-01 00:00:00
abstract::Accessing patient's veins for drug level sampling is not always feasible. The use of capillary sampling techniques is often utilized when venous access is hampered. In the therapeutic monitoring of patients, unexpected drug level results often occur that can be caused by a number of different factors. The possibility ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199005000-00009
更新日期:1990-05-01 00:00:00
abstract::The prevalence of gestational ethanol exposure and subsequent fetal exposure has been assessed in a cohort of mother-infant dyads in a Mediterranean city (Barcelona, Spain) by meconium analysis of fatty acid ethyl esters (FAEEs) after showing in this population a high prevalence of meconium opiates (8.7%), cocaine (4....
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31816a8657
更新日期:2008-04-01 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::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:OBJECTIVES:The objective of the present study was to perform an external evaluation of published linezolid population pharmacokinetic and pharmacodynamic models, in order to evaluate the predictive performance using an independent dataset. Another aim was to offer an elegant environment for display and simulation of bo...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000816
更新日期:2020-09-28 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 authors report the use of high-performance liquid chromatography-electrospray-tandem mass spectrometry (HPLC-ESI-MS/MS) for the quantification of indomethacin (IND) in plasma with microscale sample preparation. Plasma samples (100 microL) and mefanamic acid (internal standard [IS]), buffered to pH 3.5, were prepar...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199812000-00020
更新日期:1998-12-01 00:00:00
abstract::Two published case reports showed that addition of risperidone (1 and 2 mg/d) to a clozapine treatment resulted in a strong increase of clozapine plasma levels. As clozapine is metabolized by cytochrome P450 isozymes, a study was initiated to assess the in vivo interaction potential of risperidone on various cytochrom...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200106000-00008
更新日期:2001-06-01 00:00:00
abstract::Most recent cyclosporine (CsA) pharmacokinetic (PK) studies have focused on noncompartmental analysis. Because CsA undergoes significant first-pass elimination after oral dosing, the most appropriate compartment model may need to take this process into account for the construction of a valid population PK model for Sa...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199804000-00006
更新日期:1998-04-01 00:00:00
abstract::The binding characteristics of the antiepileptic agent and teratogen valproic acid for human serum and human placenta were investigated utilizing equilibrium dialysis of the drugs in serum and in homogenates of whole placenta so that the transplacental transfer of the drug could be better defined. A low-capacity, high...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/01.ftd.0000158077.07836.9a
更新日期:2005-06-01 00:00:00
abstract::To evaluate the reliability and practical use of saliva for therapeutic drug monitoring of the antifungal agent voriconazole in immunocompromised patients, a paired-sample study was conducted. Plasma and saliva trough levels were measured in seven children and nine adults who required treatment for the prevention or t...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,多中心研究
doi:10.1097/FTD.0b013e3181cff20d
更新日期:2010-04-01 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:BACKGROUND:Antiepileptic drug therapeutic regimens often need to be adjusted individually on the basis of serum assays. We aimed to develop a quantitative, fast, and sensitive liquid chromatography-tandem mass spectrometry method to simultaneously analyze carbamazepine, oxcarbazepine, and the 10-11 epoxide carbamazepin...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3182425168
更新日期:2012-02-01 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:OBJECTIVE:The aim of the study is to characterize the pharmacokinetics and the gastrointestinal side effect profiles of enteric-coated mycophenolate sodium (EC-MPS) in de novo kidney transplant patients of Hispanic ethnicity. MATERIALS AND METHODS:The pharmacokinetic study of EC-MPS was conducted in 11 de novo kidney ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31820271c3
更新日期:2011-02-01 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:BACKGROUND:Despite significant interindividual variability in prednisolone pharmacokinetics and potentially serious consequences with inadequate or excessive exposure, monitoring of prednisolone levels is not employed to guide therapy. As ultrahigh-performance liquid chromatography-tandem mass spectrometry methods can ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31829daae4
更新日期:2014-02-01 00:00:00
abstract::Despite its known teratogenic effects, thalidomide has been used to treat a variety of diseases ranging from alleviation of autoimmune disorders to prevention of metastasis of cancers. The exact method of action of thalidomide and its derivatives is still under investigation. Thalidomide undergoes very little metaboli...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200202000-00017
更新日期:2002-02-01 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::A sensitive and specific direct-injection high-performance liquid chromatography-atmospheric pressure chemical ionization tandem mass-spectrometry (HPLC-APCI-MS-MS) method has been developed for the rapid identification and quantitation of seven tricyclic antidepressants-amitriptyline, nortriptyline, doxepin, dosulepi...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200208000-00013
更新日期:2002-08-01 00:00:00
abstract::A simple and sensitive method is presented for the determination of gold in various biological matrices by flameless atomic absorption spectrometry (FAAS). The effects of the biological media on the atomic absorption of gold and the application of some of the important fundamental principles in relation to the measure...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198206000-00011
更新日期:1982-01-01 00:00:00