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 patients "poor metabolizer" phenotype status, and thus reduce interindividual pharmacokinetic variability of midazolam, a well-known CYP3A substrate. Intravenous bolus midazolam at doses of 2.5 mg and 1 mg were administered to 28 and 29 patients with cancer with and without co-administration of 200 mg of oral ketoconazole twice per day respectively for 3 days, starting 1 day before midazolam. Pharmacokinetic analyses of midazolam on both groups were derived using noncompartmental methods and compared. The mean clearance (CL) of midazolam was reduced 6 times by ketoconazole. Midazolam CL were normally distributed in both groups, and ranged from 1.7 to 51.9 and 1.4 to 8.2 L/hour in the control and ketoconazole groups, respectively, corresponding to a 7-fold reduction in dispersion between the 2 groups. Area-under-the-curve variability was reduced by >100%. A limited sampling model consisting of time points at 15 and 300 minutes was validated as a phenotype for CYP3A activity to facilitate the use of midazolam as a probe drug for CYP3A activity. Potent inhibition of CYP3A by ketoconazole reduced midazolam CL and area-under-the-curve variability, allowing for more precise achievement of therapeutic target drug exposure. Prospective evaluation of this approach, together with dose adjustment based on limited sampling, seems warranted.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Tham LS,Lee HS,Wang L,Yong WP,Fan L,Ong AB,Sukri N,Soo R,Lee SC,Goh BCdoi
10.1097/01.ftd.0000194497.55269.d9subject
Has Abstractpub_date
2006-04-01 00:00:00pages
255-61issue
2eissn
0163-4356issn
1536-3694pii
00007691-200604000-00018journal_volume
28pub_type
杂志文章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:BACKGROUND:Lacosamide (LCM) is one of the newer antiepileptic drugs (AEDs) licensed as add-on treatment for partial epilepsy. Data on LCM pharmacokinetics and interactions are limited and partly contradictory. The purpose of this study was to assess the effect of concomitant AED therapy on steady state plasma concentra...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,随机对照试验
doi:10.1097/FTD.0b013e318290eacc
更新日期:2013-12-01 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::Two hundred milligrams of valproic acid (VPA) was administered orally to seven healthy adults at 9:00 and 21:00 h for 5 consecutive days, including the morning dose on day 6. On the sixth day, blood samples were drawn at 0, 0.17, 0.33, 0.5, 0.75, 1, 1.5, 3, and 6 h after the morning dose. Binding of VPA to serum prote...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199202000-00009
更新日期:1992-02-01 00:00:00
abstract::The in vitro stability of cocaine (COC) was monitored in fresh whole blood and plasma stabilized with potassium fluoride (0.25%) for as long as 15 days. The samples were stored at 4 degreesC, 20 degreesC and 40 degreesC. Additionally, fresh plasma samples containing either benzoylecgonine (BZE), ecgonine methyl ester ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200104000-00014
更新日期:2001-04-01 00:00:00
abstract::To interpret blood levels of tricyclic antidepressants, we studied the distributions of amitriptyline and nortriptyline in human blood and explored their control by plasma factors. Each compound (300 ng/ml) was added to whole adult blood and to cord blood with decreased alpha-1-glycoprotein (AGP). Drugs (250 ng/ml) we...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199308000-00002
更新日期:1993-08-01 00:00:00
abstract:BACKGROUND:The aim of this study was to conduct a population pharmacokinetic (PK) analysis of meropenem and to explore the optimal dosing strategy for meropenem in critically ill patients with acute kidney injury receiving treatment with continuous hemodiafiltration (CHDF). METHODS:Blood samples were obtained on days ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000741
更新日期:2020-08-01 00:00:00
abstract::A sensitive method is described for the simultaneous determination of mebendazole and hydroxymebendazole using flubendazole as an internal standard. The analytes were isolated with a single chloroform extraction from 1.0 ml of alkalinized plasma or cyst liquid samples. Separation and quantitation were performed with h...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198406000-00015
更新日期:1984-01-01 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:Because of its superior sensitivity and specificity, multianalyte high-performance liquid chromatography coupled with tandem mass spectrometry has become the gold standard in clinical toxicology. Although several qualitative and quantitative liquid chromatography coupled with tandem mass spectrometry assays ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000429
更新日期:2017-10-01 00:00:00
abstract::The use of therapeutic drug monitoring strategies for cyclosporin (CsA) has evolved markedly in recent years since previous consensus guidelines were presented. Apart from the introduction of some new methods, the major change has been the shift away from the traditional predose/trough (C0) sample. The most popular al...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200404000-00025
更新日期:2004-04-01 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::Tyrosine kinase inhibitors are the standard of care for the treatment of chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia. Dasatinib is a second-generation tyrosine kinase inhibitor that has been shown to be efficacious in treatment of patients with chronic myeloid leukemia or ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/FTD.0b013e3181f4d9c5
更新日期:2010-12-01 00:00:00
abstract:BACKGROUND:Pentobarbital is used for management of intractable seizures and for reducing elevated intracranial pressure. Dosing of pentobarbital can be aided by therapeutic drug monitoring (TDM). There is no commercially available automated assay for measurement of pentobarbital serum/plasma concentrations; consequentl...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000217
更新日期:2015-12-01 00:00:00
abstract::Lidocaine has a concentration-dependent effect on seizures. At lower concentrations it has anticonvulsant properties, whereas concentrations above 15 microg/mL frequently result in seizures in laboratory animals and man. Seizures induced by lidocaine in experimental conditions invariably start in the amygdala. Despite...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-200006000-00014
更新日期:2000-06-01 00:00:00
abstract::OKT3 is a murine monoclonal antibody of the immunoglobulin IgG2a isotype. The target of OKT3, CD3, is a 17-20 kilodalton (kD) molecule that is part of a multimolecular complex found only on mature T cells and medullary thymocytes. This complex is uniquely situated next to the T-cell receptor for antigen. An interactio...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-199512000-00012
更新日期:1995-12-01 00:00:00
abstract::In a phase I-II study, the authors evaluated the intracellular pharmacokinetics, toxicity, and efficiency of a high dose of mitoxantrone given as first induction in acute non-lymphocytic leukemia. Twenty-two patients with previously untreated de novo ANLL were included and received 30 or 40 mg/m2 mitoxantrone on day 1...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-199812000-00010
更新日期:1998-12-01 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::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::Specific chromatographic methods for the measurement of cyclosporin A, tacrolimus, sirolimus, and everolimus blood levels in patients with organ transplants are time consuming when large numbers of samples must be processed. The authors developed a robust and fast (1 minute) online solid-phase extraction liquid chroma...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181c49a00
更新日期:2010-02-01 00:00:00
abstract::Atractyloside poisoning is an infrequent but often fatal form of herbal poisoning, which occurs worldwide but especially in Africa and the Mediterranean regions. The primary mechanism of atractyloside poisoning is known to be inhibition of the mitochondrial ADP transporter. Poisoning in humans may present with either ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-200012000-00001
更新日期:2000-12-01 00:00:00
abstract::The aim of this study was to assess dose-related steady-state serum concentrations of olanzapine (OLZ) and its metabolites N-desmethyl OLZ (DMO) and 2-hydroxymethyl OLZ (2-OH-OLZ) (assessed by high-performance liquid chromatography) in 122 child and adolescent psychiatric patients (age 16.9 +/- 2.2, range, 10-21 years...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/01.ftd.0000249950.75462.7f
更新日期:2006-12-01 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
abstract::Fifteen patients were studied during short-term (5 days at 10-15 mg/m2/day) or long-term (5-104 days at 3 mg/m2/day) doxorubicin infusion. Levels of doxorubicin and metabolites in serum and 24-h timed urine collections were determined by high-performance liquid chromatography. Quantifiable anthracycline levels were id...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-198901000-00002
更新日期:1989-01-01 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::5-Methoxy-N,N-dialkyltryptamines are tryptamine derivatives that possess strong hallucinogenic effects. Because of their escalating popularity and potent physiological effects, an increasing number of acute poisoning cases have been reported in various countries. For their metabolism in humans, only a few studies have...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181dcb40c
更新日期:2010-06-01 00:00:00
abstract::The analysis of quinine in whole blood, plasma, urine, and samples dried on filter paper is described. Extraction was made with toluene followed by back-extraction into phosphate buffer. A reversed-phase liquid chromatography system with fluorescence detection was used. The within-day coefficient of variation of the m...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199308000-00012
更新日期:1993-08-01 00:00:00
abstract::Eight subjects were studied in a randomized crossover design to determine the effect of aluminum-magnesium hydroxide (AMH), calcium carbonate (CC), and aluminum hydroxide-magnesium trisilicate (AHMT) on the bioavailability of a single, 600-mg dose of phenytoin administered orally. Each subject received phenytoin alone...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00007691-198104000-00003
更新日期:1981-01-01 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::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