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 were analyzed according to a one-compartment model using the nonlinear mixed effect modelling program. The influences of origin (Germany or Spain), sex, age, total body weight, and comedication with valproic acid (VPA), levetiracetam, and enzyme-inducing antiepileptic drugs (phenobarbital [PB], phenytoin [PHT], primidone [PRM], and carbamazepine [CBZ]) were investigated using step-wise generalized additive modelling. The final regression model for LTG clearance (CL) was as follows: CL(L/h) = 0.028*total body weight*e(-0.713*VPA)*e0.663*PHT*e0.588*(PB or PRM)*e0.467*CBZ*e0.864*IND, where IND refers to two or more inducers added to LTG treatment; this factor as well as VPA, PHT, PB, PRM, and CBZ take a value of zero or one according to their absence or presence, respectively. The administration of inducers led to a significant increase in mean LTG CL (values of 0.045-0.070 L/h/kg vs. 0.028 L/h/kg being reached in monotherapy), whereas VPA led to a significant decrease in CL (0.014 L/h/kg). Thus, comedication with these analyzed drugs can partly explain the interindividual variability in population LTG CL, which decreased from the basic model by more than 40%. The proposed model may be very useful for clinicians in establishing initial LTG dosage guidelines. However, the interindividual variability remaining in the final model (clearance coefficient of variation close to 30%) make these a priori dosage predictions imprecise and justifies the need for LTG plasma level monitoring to optimize dosage regimens. Thus, this final model allows easy implementation in clinical pharmacokinetic software and its application in dosage individualization using the Bayesian approach.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Rivas N,Buelga DS,Elger CE,Santos-Borbujo J,Otero MJ,Domínguez-Gil A,García MJdoi
10.1097/FTD.0b013e31817fd4d4subject
Has Abstractpub_date
2008-08-01 00:00:00pages
483-9issue
4eissn
0163-4356issn
1536-3694journal_volume
30pub_type
杂志文章abstract::Digoxin and gentamicin are widely used in pediatric medicine, and therapeutic monitoring is mandatory because of their narrow margin of safety and wide interpatient and intrapatient pharmacokinetic variabilities. Saliva sampling may be of potential interest, especially in children, in whom blood sampling is often diff...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199806000-00003
更新日期:1998-06-01 00:00:00
abstract::The treatment of rheumatoid arthritis (RA) has largely improved in the biopharmaceutical era. These compounds, primarily tumor necrosis factor (TNF) inhibitors, are effective, but some patients may show poor response, sometimes because of the presence of antidrug antibodies (ADAs). In some instances, clinicians may in...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/FTD.0000000000000421
更新日期:2017-08-01 00:00:00
abstract::A minority of athletes continues to use prohibited drugs in sports to enhance performance. Athletes discovered using these drugs can be subject to severe penalties, often resulting in media and public scrutiny, especially at major events such as the Olympic Games. The International Olympic Committee (IOC) has set out ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-200002000-00022
更新日期:2000-02-01 00:00:00
abstract:BACKGROUND:We report a feasibility study based on our large-scale experience with mycophenolate mofetil dose adjustment based on mycophenolic acid interdose area under the curve (AUC) in renal transplant patients. METHODS:Between 2005 and 2010, 13,930 requests for 7090 different patients (outside any clinical trial) w...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31821633a6
更新日期:2011-06-01 00:00:00
abstract::An isocratic, high-performance liquid chromatography method has been developed for simultaneous determination of the tricyclic antidepressant clomipramine and six metabolites: desmethylclomipramine, 2- and 8-hydroxy-clomipramine, 2- and 8-hydroxydesmethylclomipramine and didesmethyl-clomipramine in plasma and urine. I...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199304000-00010
更新日期:1993-04-01 00:00:00
abstract:BACKGROUND:Current gentamicin dosing algorithms in adult populations target a high peak concentration (Cmax) assuring efficacy and a drug-free period (concentration <0.5 mg/L) preventing toxicity. In contrast, gentamicin-based regimens in neonatal sepsis often aim for lower peak levels and trough concentrations of 0.5-...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000283
更新日期:2016-06-01 00:00:00
abstract::It is generally accepted that chemical testing of biologic fluids is the most objective means of diagnosis of drug use. The presence of a drug analyte in a biologic specimen can be used to document exposure. The standard for drug testing in toxicology is an immunoassay screen conducted on a urine sample, followed by c...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/00007691-200204000-00006
更新日期:2002-04-01 00:00:00
abstract::During once-daily dosing regimens of aminoglycosides, administration of large single doses results in high peak levels and low 24-h trough levels. However, commercial assays for monitoring aminoglycoside levels are designed to cover the smaller range of serum concentrations usually observed during multiple daily dosin...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/00007691-199504000-00005
更新日期:1995-04-01 00:00:00
abstract:OBJECTIVE:This naturalistic therapeutic drug monitoring (TDM) study aimed to evaluate the relationship between dosage, serum concentration, and clinical outcome in children and adolescents treated with the serotonin reuptake inhibitor sertraline for different indications. METHODS:Steady-state trough serum concentratio...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0b013e31827a1aad
更新日期:2013-02-01 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::With the introduction of a cyclosporin monitoring strategy based on the use of a sample collected 2 hours after dosing (C2) rather than the predose sample (C0), there was concern that the differences in blood cyclosporin results from the various assay systems would result in assay-specific target ranges for C2 monitor...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/00007691-200304000-00005
更新日期:2003-04-01 00:00:00
abstract:BACKGROUND:The pharmacokinetics of long-acting intramuscular paliperidone in a naturalistic setting is not well documented. The objective of this study was to investigate the relationship between dose and serum concentrations of paliperidone using data from a routine therapeutic drug monitoring service. METHODS:Serum ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000457
更新日期:2017-12-01 00:00:00
abstract::The purpose of the present study was to examine the effects of rifampicin on the single oral dose pharmacokinetics and pharmacodynamics of brotizolam. Thirteen healthy male volunteers received rifampicin 450 mg/day, or matched placebo, for 7 days in a double-blind randomized crossover manner. On the sixth day they rec...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,随机对照试验
doi:10.1097/01.ftd.0000200010.33430.0e
更新日期:2006-06-01 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::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::The authors describe a case of furosemide possibly inhibiting the hypoprothrombinemic effect of warfarin. The initiation of furosemide dosing in a patient receiving a stable dose of warfarin was associated with an 28% decrease in the international normalized ration (INR). Using normal volunteers, two previous controll...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199706000-00019
更新日期:1997-06-01 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:BACKGROUND:Infliximab is a chimeric monoclonal antibody that binds to human tumor necrosis factor alpha and which is approved for refractory spondyloarthritis (SpA). Individual adjustment of infliximab dosage may help to improve the therapeutic response in SpA. We investigated whether a knowledge of infliximab serum co...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/FTD.0b013e318224f83d
更新日期:2011-08-01 00:00:00
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)pharmacod...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,随机对照试验
doi:10.1097/FTD.0b013e3181b1dd76
更新日期:2009-10-01 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::The authors evaluated an integrated approach for the screening of drugs in biosamples consisting of gas chromatography/mass spectrometry analysis of serum or whole blood (SB/GC-MS) and of high-performance liquid chromatographic and ultraviolet (HPLC-UV) analysis of urine with the REMEDi HS Biorad system (U/REM) (Bio-r...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200106000-00018
更新日期:2001-06-01 00:00:00
abstract:BACKGROUND:Analysis of residual gene expression of the nuclear factor of activated T cell (NFAT)-regulated genes has been developed as a pharmacodynamic biomarker to monitor therapy with calcineurin inhibitors. The availability of commercial primer sets (Search-LC) and the well-established assay protocol makes this bio...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000340
更新日期:2016-12-01 00:00:00
abstract::A population pharmacokinetic model was developed after administration of orogastric and/or intravenous indomethacin for the treatment of patent ductus arteriosus in preterm infants. Plasma indomethacin concentrations (n=227) were obtained from 90 preterm infants of median gestational age 27 weeks, mean postnatal age o...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/FTD.0b013e31815b3e13
更新日期:2007-12-01 00:00:00
abstract::A simple and sensitive column-switching high-performance liquid chromatographic method for the simultaneous determination of itraconazole (ITZ) and its active metabolite, hydroxyitraconazole (HIT) in human plasma is described. ITZ, HIT, and an internal standard, R051012, were extracted from 1 mL of alkalinized plasma ...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/00007691-200608000-00007
更新日期:2006-08-01 00:00:00
abstract::For the accuracy of routine monitoring of digoxin and digitoxin it seems important to get information on the cross-reactivity of endogenous digitalis-like substances (EDLS). To obtain EDLS, urine was passed on Sep-Pak columns and eluted in fractions by increasing concentrations of acetonitrile. Dilution series of two ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1988-01-01 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::Designer drugs of the methylenedioxyphenylalkylamine type are increasingly abused. Studies on their metabolism in humans are necessary to develop a reliable gas chromatography--mass spectrometry (GC-MS) screening procedure. Such a method must allow their detection in urine for drug testing in clinical and forensic tox...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199608000-00027
更新日期:1996-08-01 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::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::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