Abstract:
:This study was undertaken to model the relationship between clonazepam plasma concentrations and a central nervous system adverse effect (impairment of the psychomotor performance) following the oral administration of immediate-release tablets of clonazepam in healthy volunteers. Such a (P)pharmacokinetic/(P)pharmacodynamic (PK/PD) study is important to interpret properly the consequences of determined levels of plasma concentrations of psychoactive therapeutic drugs reported to be involved in road-traffic accidents. Twenty-three male subjects received a single oral dose of 4 mg clonazepam. Plasma concentration, determined by on-line solid phase extraction coupled with high-performance liquid chromatography tandem mass spectrometry, and psychomotor performance, quantified through the Digit Symbol Substitution Test, were monitored for 72 hours. A 2-compartment open model with first order absorption and lag-time better fitted the plasma clonazepam concentrations. Clonazepam decreased the psychomotor performance by 72 +/- 3.7% (observed maximum effect), 1.5 to 4 hours (25th-75th percentile) after drug administration. A simultaneous population PK/PD model based on a sigmoid Emax model with time-dependent tolerance described well the time course of effect. Such acute tolerance could minimize the risk of accident as a result of impairment of motor skill after a single dose of clonazepam. However, an individual analysis of the data revealed a great interindividual variation in the relationship between clonazepam effect and plasma concentration, indicating that the phenomenon of acute tolerance can be predicted at a population, but not individual, level.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
dos Santos FM,Gonçalves JC,Caminha R,da Silveira GE,Neves CS,Gram KR,Ferreira CT,Jacqmin P,Noël Fdoi
10.1097/FTD.0b013e3181b1dd76subject
Has Abstractpub_date
2009-10-01 00:00:00pages
566-74issue
5eissn
0163-4356issn
1536-3694journal_volume
31pub_type
杂志文章,随机对照试验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::A noninstrumented enzyme immunochromatography (EIC) method for monitoring carbamazepine using whole blood was compared to the enzyme-multiplied immunoassay technique (EMIT), fluorescence polarization immunoassay (FPIA), and high-performance liquid chromatography (HPLC). Samples from 74 patients were evaluated in the c...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract::A rapid and reliable micro procedure for the high pressure liquid chromatographic analysis of cimetidine. N"-cyano-N-methyl-N'-[2-[[(5-methyl-1H-imidazol-4-yl)methyl]thio]ethyl]guanidine, in serum or plasma is described. The percentage analytical recovery of cimetidine and internal standard (beta-hydroxypropyl-theophy...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-197901030-00010
更新日期:1979-01-01 00:00:00
abstract:BACKGROUND:The combination of trimethoprim (TMP) and sulfamethoxazole (SMX) is used to treat a number of bacterial infections. TMP/SMX concentrations in serum are conventionally monitored using high-performance liquid chromatography (HPLC) or liquid chromatography tandem mass spectrometry. These methods require laborio...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000785
更新日期:2020-10-01 00:00:00
abstract::Phenytoin is an anticonvulsant that requires therapeutic drug monitoring. Recently, Bayer HealthCare, Diagnostics Division released a turbidimetric immunoassay of phenytoin on the ADVIA 1650 analyzer. We evaluated the analytic performance of this assay by comparing values obtained in 52 patients receiving Phenytoin us...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/01.ftd.0000164315.13825.dd
更新日期:2005-06-01 00:00:00
abstract:BACKGROUND:The objective of this study was to investigate the serum concentrations of olanzapine in relation to age, sex, and other factors in Chinese patients aged between 10 and 90 years. METHODS:Data for 884 olanzapine patients, deposited between 2016 and 2017, were retrieved from the therapeutic drug monitoring da...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000738
更新日期:2020-08-01 00:00:00
abstract::This case report highlights a very rare adverse drug reaction caused by oral aripiprazole resulting in severe hypoglycemia. A 72-year-old-male patient suffering from Parkinson disease on prolonged carbidopa plus levodopa combination therapy (carbidopa 25 mg plus levodopa 100 mg, thrice daily) for 1.3 years was recentl...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/FTD.0b013e3182557d10
更新日期:2012-06-01 00:00:00
abstract::There are a number of effective but highly toxic drugs that exhibit a narrow therapeutic index and marked interpatient pharmacokinetic variability. Individualized therapy with such drugs requires therapeutic drug monitoring (TDM) to obtain the desired clinical effects safely. Cost-effectiveness analysis in health care...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-200502000-00004
更新日期:2005-02-01 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::The DuPont theophylline assay reagent kit, a particle-enhanced turbidimetric inhibition immunoassay (PETINIA) method adapted for use on a centrifugal fast analyzer, was evaluated. It was compared with fluorescence polarization immunoassay (FPIA). Day-to-day precision was 4.7% at 6.8 micrograms/ml, and 3.3% at 26.6 mic...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198606000-00019
更新日期:1986-01-01 00:00:00
abstract::Epilepsy is characterized by seizures recurring at interindividually differing time intervals. It may be difficult to assess drug response if time intervals between seizures are long. Thus, the existence of surrogate parameters that could be used to reliably identify drug efficacy and tolerability at an early stage an...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/FTD.0000000000000623
更新日期:2019-04-01 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::Given the high prevalence of the use of medications in daily practice and the large number of people taking antirheumatic agents, the risk of drug-drug interactions and of hepatotoxicity is of concern. Both old and new compounds show such a risk. Nonsteroidal antinflammatory drugs are widely used drugs with potential ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/FTD.0b013e31826a6306
更新日期:2012-12-01 00:00:00
abstract::The immunosuppressive potential of mycophenolic acid (MPA) correlates well with MPA exposure [area under the concentration-time curve (AUC)]. Monitoring MPA AUC is important and helpful for maintaining the efficacy of mycophenolate mofetil while minimizing its side effects, but full MPA AUC monitoring is laborious, co...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181559f8a
更新日期:2007-10-01 00:00:00
abstract::An isocratic, high-performance liquid chromatography method has been developed for simultaneous determination of the oral antidiabetic tolbutamide and two of its metabolites, 4-hydroxytolbutamide and carboxytolbutamide, in human plasma and urine. The method was based on simple one-step liquid-liquid extraction with te...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199912000-00015
更新日期:1999-12-01 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::Mycophenolate mofetil (MMF) is the first drug approved for the prevention of renal allograft rejection in the United States in the last 10 years. MMF is the morpholinoethyl ester of mycophenolic acid (MPA) and is a selective, reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH), an enzyme that is critic...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199608000-00007
更新日期:1996-08-01 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::Hair testing procedures allow a cumulative reflection of long-term drug abuse and are useful as a test for compliance in clinical toxicology. In the present study, liquid chromatography coupled with tandem mass spectrometry was used to determine analgesic opioid drugs in hair samples. The procedure used a simple metha...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e318155a329
更新日期:2007-10-01 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::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 authors describe a reverse-phase high-performance liquid chromatography-electrospray-tandem mass spectrometry method for the measurement of nicotine in human plasma. Samples (500 microL) with added deuterium-labeled d3-nicotine as an internal standard (IS) were treated with a 2-step process of ether extraction (6 ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200410000-00015
更新日期:2004-10-01 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::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::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::The commonly used immunosuppressive regimen after orthotopic heart transplantation consists of cyclosporine (CsA), azathioprine (AZA), and steroids. Although AZA therapy is generally regarded as unproblematic, its use can be associated with severe side effects, particularly myelosuppression. Since AZA is a prodrug, wh...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-199606000-00002
更新日期:1996-06-01 00:00:00
abstract:BACKGROUND:Hair analysis of ethyl glucuronide (EtG) has become, beside fatty acid ethyl ester, a valuable marker for the detection of moderate and chronic excessive alcohol consumption. So far, only few studies exist about the influence of cosmetic treatment on EtG content in hair. The aim of this study was to evaluate...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31828ca246
更新日期:2013-08-01 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::Studies of the antidepressant effect and pharmacokinetics of citalopram have been performed in adults, but the effects on children and adolescents have only been studied to a minor extent despite its increasing use in these age groups. The aim of this study was to investigate a group of adolescents treated for depress...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200112000-00011
更新日期:2001-12-01 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