Abstract:
:The authors report preliminary findings on the potential contribution of CYP2C19 isoenzyme to the human metabolism of N-desmethylclobazam (N-CLB), the main active metabolite of clobazam (CLB), a benzodiazepine frequently used as add-on therapy in patients with refractory epilepsy. Two children on CLB treatment showing extremely high plasma concentration/dose ratio (C/D) of N-CLB and metabolite/parent drug ratio (N-CLB/CLB), suggestive of a putative poor metabolizer (PM) phenotype, were tested for CYP2C19 polymorphisms. Eleven epileptic patients on stable CLB therapy were included for reference values of CLB and N-CLB metabolic variables and tested for possible CYP2C19 polymorphisms. Detection of the CYP2C19*2, CYP2C19*3, and CYP2C19*4 mutations was performed in the genomic DNA by PCR amplification and enzyme digestion procedures. In the two presumed CYP2C19 PM patients, the N-CLB/CLB ratio was 10- to 27-fold higher than matched median values of the control epileptic patients. According to CYP2C19 genotyping, one patient was homozygous for CYP2C19*2, while the second presented only one copy of the same mutation, a genotype also found in three control patients. These observations provide further indirect in vivo evidence of CYP2C19 isoenzyme involvement in the metabolism of the CLB main metabolite. According to genotyping, subjects carrying one or two copies of the defective CYP2C19*2 allele might develop markedly elevated steady-state plasma concentrations of N-CLB and be at higher risk of adverse effects.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Contin M,Sangiorgi S,Riva R,Parmeggiani A,Albani F,Baruzzi Adoi
10.1097/00007691-200212000-00009subject
Has Abstractpub_date
2002-12-01 00:00:00pages
737-41issue
6eissn
0163-4356issn
1536-3694journal_volume
24pub_type
杂志文章abstract::This study develops a population pharmacokinetic model for lamotrigine (LTG) in Spanish and German patients diagnosed with epilepsy. LTG steady-state plasma concentration data from therapeutic drug monitoring were collected retrospectively from 600 patients, with a total of 1699 plasma drug concentrations. The data we...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31817fd4d4
更新日期:2008-08-01 00:00:00
abstract::In a prospective study over 6 months, the relationship between serum lipid parameters and CsA whole blood trough concentrations was investigated in 39 renal transplant recipients receiving a triple immunosuppressive therapy with cyclosporin (CsA), azathioprine and prednisone. CsA trough concentrations were measured wi...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199704000-00004
更新日期:1997-04-01 00:00:00
abstract::Rapamycin (RAPA) is a new immunosuppressive drug with a potency similar to that of FK506 and up to a 100-fold greater than that of cyclosporine (CsA). RAPA has shown to be efficacious in the prolongation of allograft survival in a number of animal models. In early studies, RAPA was administered on a dose/weight basis,...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-199312000-00004
更新日期:1993-12-01 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::The immunosuppressant mycophenolic acid (MPA) used for solid organ transplantation is predominantly metabolized to a pharmacologically inactive phenolic glucuronide (MPAG) and, to a lesser extent, to the pharmacologically active acyl glucuronide (AcMPAG). The recently introduced CEDIA Mycophenolic Acid Assay from Micr...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181cc342a
更新日期:2010-02-01 00:00:00
abstract::A radioimmunoassay (RIA) procedure for the determination of sulforidazine in human plasma was developed using an antiserum raised in rabbits immunized with N-(2-carboxyethyl)desmethylsulforidazine-porcine thyroglobulin conjugate. The RIA procedure can measure as low as 40 pg of sulforidazine in a 200-microliter human ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198802000-00016
更新日期:1988-01-01 00:00:00
abstract::It has been suggested that lamotrigine (LTG) may enhance the toxicity of carbamazepine (CBZ) by increasing the concentration of the active metabolite carbamazepine-10,11-epoxide (CBZ-E) in adult patients. The authors investigated this hypothesis in an add-on study in 11 children and 3 adolescents, aged 6-22 years, who...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199710000-00002
更新日期:1997-10-01 00:00:00
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::Eight patients are described who displayed excessive concentrations of nortriptyline, imipramine, or clomipramine on routine blood level monitoring. Under these conditions, the patients did not respond to the treatment. All patients were markedly improved when the daily dosage of the antidepressant was reduced with a ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1989-01-01 00:00:00
abstract:BACKGROUND:SB2, an infliximab (IFX) biosimilar to the reference infliximab (R.I.) product (Remicade), received approval in the European Union for all IFX indications. Many decision algorithms based on the measurement of IFX trough levels and antibodies to infliximab are being increasingly used to optimize IFX treatment...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000565
更新日期:2018-12-01 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::The postulated therapeutic activity of nortriptyline metabolites has prompted investigation of dosage adjustments based on plasma levels of nortriptyline (NT) and its metabolites. The method assumes that metabolite concentrations vary independently of nortriptyline concentrations among patients. This study tests that ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198905000-00001
更新日期:1989-01-01 00:00:00
abstract::Two separate studies were carried out to assess the effect of valproic acid on the steady-state plasma concentrations of clozapine and its major metabolites norclozapine and clozapine N-oxide in psychotic patients. In the first study, concentrations of clozapine and metabolites were compared between patients treated w...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-199906000-00017
更新日期:1999-06-01 00:00:00
abstract:BACKGROUND:Fosphenytoin, the diphosphate ester salt of phenytoin, is widely used to treat status epilepticus. The aim of this study was to develop a population pharmacokinetic (PPK) model to describe serum phenytoin concentrations after the intravenous administration of fosphenytoin in adult and elderly epileptic patie...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000651
更新日期:2019-10-01 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::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::During the past two decades, in association with the commencement of chronic dialysis therapy and prolongation of the uremic state, aluminum toxicity has represented a major cause of morbidity and mortality in uremic patients. The uremic patient has been found to be at higher risk of aluminum loading and toxicity from...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-199312000-00025
更新日期:1993-12-01 00:00:00
abstract:BACKGROUND:The once-daily formulation of tacrolimus has been reported to exhibit the same efficacy and safety profile as compared with the immediate-release form administered twice daily. However, as a result of differences in their pharmacokinetic (PK) profile, the PK models or Bayesian estimators (MAP-BE) previously ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e3181cc70db
更新日期:2010-04-01 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::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::Oral posaconazole (PSZ), an azole antifungal drug, was recently introduced for the treatment of invasive fungal infections. The prescription of PSZ together with the immunosuppressant tacrolimus (TRL) was evaluated in 14 lung transplant patients with cystic fibrosis. PSZ inhibited CYP3A4 TRL metabolism, resulting in a...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31819de6fd
更新日期:2009-06-01 00:00:00
abstract::Gabapentin is used in analgesic treatment of neuropathic pain, and large interindividual variation has been observed in the pharmacokinetics (PK) of the drug. The aim of this study was to develop a population PK model for gabapentin appropriate for monitoring patients with neuropathic pain and for individualizing thei...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e318194767d
更新日期:2009-02-01 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:BACKGROUND:Several factors such as low therapeutic index, large interindividual variability in systemic exposure, and the relationships between exposure and toxicity for sorafenib could justify its therapeutic drug monitoring (TDM). To support TDM, a selective and precise high-performance liquid chromatography with ult...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000027
更新日期:2014-06-01 00:00:00
abstract::Simplified pharmacokinetic methods have been used to estimate caffeine clearance in subjects with liver disease. There is a need to have a reliable, easy to implement method for research and possible clinical use. This study evaluates the use of Bayesian pharmacokinetic forecasting techniques to estimate caffeine clea...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199802000-00015
更新日期:1998-02-01 00:00:00
abstract::Steady-state serum concentrations of quetiapine were recorded in 62 psychiatric patients under routine conditions. Doses were administered twice daily, and serum quetiapine levels were measured in the morning about 12 hours after the last dose. Eight patients were in monotherapy, whereas the rest received various addi...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-200410000-00005
更新日期:2004-10-01 00:00:00
abstract::For many drugs, therapeutic drug monitoring (TDM) has become widely available and accepted as an important component of clinical decision-making in the intensive care nursery setting. This review analyzes the potential factors that can either expand or restrict neonatal TDM. A case is made for the development of pharm...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-199007000-00002
更新日期:1990-07-01 00:00:00
abstract:BACKGROUND:Several reports of loss of efficacy or adverse effects have been described after generic substitution of antipsychotics. To date, studies comparing serum drug levels in patients switched to generic antipsychotics in a standard clinical setting are lacking. The aim of this study was to investigate if switchin...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000211
更新日期:2015-12-01 00:00:00
abstract::The authors refer to their experience with alternative matrices to supervise the methadone therapy of heroin abusers. For this purpose, hair, sweat, and urine samples were collected from 10 heroin addicts and from a control group and were submitted to gas chromatographic/mass spectroscopic analysis for methadone and i...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31811f1bbe
更新日期:2007-08-01 00:00:00
abstract:BACKGROUND:Beta-lactams are first-line antibiotics for the management of superficial infections due to burn injury. There is sparse data available on therapeutic drug monitoring (TDM) in patients with burns in a ward setting. This study was conducted to evaluate the utility of a beta-lactam TDM program in a cohort of b...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31824981a6
更新日期:2012-04-01 00:00:00