Abstract:
BACKGROUND:Busulfan dose adjustment is routinely guided by plasma concentration monitoring using 4-9 blood samples per dose adjustment, but a pharmacometric Bayesian approach could reduce this sample burden. METHODS:The authors developed a nonparametric population model with Pmetrics. They used it to simulate optimal initial busulfan dosages, and in a blinded manner, they compared dosage adjustments using the model in the BestDose software to dosage adjustments calculated by noncompartmental estimation of area under the time-concentration curve at a national reference laboratory in a cohort of patients not included in model building. RESULTS:Mean (range) age of the 53 model-building subjects was 7.8 years (0.2-19.0 years) and weight was 26.5 kg (5.6-78.0 kg), similar to nearly 120 validation subjects. There were 16.7 samples (6-26 samples) per subject to build the model. The BestDose cohort was also diverse: 10.2 years (0.25-18 years) and 46.4 kg (5.2-110.9 kg). Mean bias and imprecision of the 1-compartment model-predicted busulfan concentrations were 0.42% and 9.2%, and were similar in the validation cohorts. Initial dosages to achieve average concentrations of 600-900 ng/mL were 1.1 mg/kg (≤12 kg, 67% in the target range) and 1.0 mg/kg (>12 kg, 76% in the target range). Using all 9 concentrations after dose 1 in the Bayesian estimation of dose requirements, the mean (95% confidence interval) bias of BestDose calculations for the third dose was 0.2% (-2.4% to 2.9%, P = 0.85), compared with the standard noncompartmental method based on 9 concentrations. With 1 optimally timed concentration 15 minutes after the infusion (calculated with the authors' novel MMopt algorithm) bias was -9.2% (-16.7% to -1.5%, P = 0.02). With 2 concentrations at 15 minutes and 4 hours bias was only 1.9% (-0.3% to 4.2%, P = 0.08). CONCLUSIONS:BestDose accurately calculates busulfan intravenous dosage requirements to achieve target plasma exposures in children up to 18 years of age and 110 kg using only 2 blood samples per adjustment compared with 6-9 samples for standard noncompartmental dose calculations.
journal_name
Ther Drug Monitjournal_title
Therapeutic drug monitoringauthors
Neely M,Philippe M,Rushing T,Fu X,van Guilder M,Bayard D,Schumitzky A,Bleyzac N,Goutelle Sdoi
10.1097/FTD.0000000000000276subject
Has Abstractpub_date
2016-06-01 00:00:00pages
332-42issue
3eissn
0163-4356issn
1536-3694journal_volume
38pub_type
杂志文章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::Studies examining associations between antidepressant response and plasma levels of bupropion and its metabolites have yielded contradictory findings. There have been no such studies in youth. This study explored such associations in 8 boys and 8 girls, age 11 to 17 years, all prescribed bupropion sustained release (S...
journal_title:Therapeutic drug monitoring
pub_type: 临床试验,杂志文章
doi:10.1097/01.ftd.0000197093.92559.7a
更新日期:2006-04-01 00:00:00
abstract::Plasma levels of 6-mercaptopurine were determined in 22 consecutive children with acute lymphoblastic leukemia on oral remission maintenance therapy during the time period of August 1984 to January 1988. Each child received the drug once daily for up to 3 years and was studied repeatedly (1-12 times). An HPLC method w...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198911000-00001
更新日期:1989-11-01 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::The use of alternative strategies to the traditional pre-dose/trough (C0) blood sampling for cyclosporine (CsA) therapeutic drug monitoring has the potential to revolutionize analytical practices which have, in many centers, been established for some 20 years. While the C0 sample has previously been recommended, curre...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200208000-00003
更新日期:2002-08-01 00:00:00
abstract::Individualized tobramycin therapy was systemically evaluated in 26 patients with gram-negative pneumonias involving Pseudomonas aeruginosa and other multiple antibiotic-resistant pathogens. Patient prognoses were classified by underlying diseases, and response was determined according to previously established criteri...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:
更新日期:1980-01-01 00:00:00
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:BACKGROUND:Tacrolimus pharmacokinetics in obese patients have been poorly studied. Herein, the authors explored the impact of obesity on tacrolimus exposure in kidney transplant recipients (KTRs) and estimated a more suitable initial dosage in this population. METHODS:A retrospective, observational, monocentric case-c...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000820
更新日期:2020-10-05 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:BACKGROUND:Busulfan (Bu) and cyclophosphamide (Cy) are frequently included in conditioning regimens before hematopoietic stem cell transplantation (HSCT). Both drugs are detoxified by glutathione transferases (GST), and GST gene variants may explain some of the interindividual variability in pharmacokinetics and drug t...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000180
更新日期:2015-08-01 00:00:00
abstract:BACKGROUND:Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD) time courses in serum and physiological and behavioral effects associated with smoking 1 or 4 "light cannabis" cigarettes were studied. Biomarkers to differentiate light cannabis versus illegal and medical cannabis use were also investigated. METHODS:Sera ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000683
更新日期:2020-02-01 00:00:00
abstract::Determination of serum concentrations of certain drugs is becoming increasingly important for optimal patient care. These drugs include many antibiotics, several antiarrhythmics, cardiac glycosides, lithium, phenytoin, some other anticonvulsants, salicylates, and theophylline. Serum level determinations can also be us...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:
更新日期:1981-01-01 00:00:00
abstract::The authors aimed to evaluate the utility of the history and clinical signs for predicting ingestion of poisons in children. A prospective cohort study was performed of all patients presenting with suspected poisoning to a pediatric emergency department over a 13-month period. Clinical data were collected on a preform...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200312000-00012
更新日期:2003-12-01 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::The authors describe a rapid, useful, specific, and very sensitive high-performance liquid chromatographic assay for the determination of fluvastatin (FV) level using atorvastatin as the internal standard (IS). After a simple deproteinization of 1.0 mL of plasma with acetonitrile, the drug and IS were extracted with t...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200302000-00013
更新日期:2003-02-01 00:00:00
abstract::In this report we describe a rapid and sensitive micromethod using high performance liquid chromatography (HPLC) with electrochemical detection (ED) to measure morphine concentration in serum or plasma. The separation of morphine and the internal standard 5-hydroxyquinoline, from interfering compounds present in plasm...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198208000-00010
更新日期:1982-01-01 00:00:00
abstract::Phenytoin binding to serum proteins and factors influencing protein binding were investigated in 38 critically ill trauma patients. In 24% of these patients, the free fraction of phenytoin was < or = 10%, whereas in 76%, the free phenytoin fraction was increased > 10%--up to 24%. Nonantiepileptic comedication, sex, or...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199404000-00005
更新日期:1994-04-01 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::Euthyroid women experience dramatic changes in their thyroid physiology in order to accommodate the presence of placental and fetal tissues. These adaptations to the pregnant state make it crucial to develop reliable trimester-specific intervals for thyroid parameters. Use of non-pregnant reference intervals could lea...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,评审
doi:10.1097/01.ftd.0000211834.41844.82
更新日期:2006-06-01 00:00:00
abstract::A comparative bioavailability study of carbamazepine (CBZ) in tablets and a syrup preparation was carried out in six volunteers, using a crossover design. Plasma and saliva samples were collected at appropriate times, and the plasma specimens were analyzed by high performance liquid chromatography for concentrations o...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-198503000-00005
更新日期:1985-01-01 00:00:00
abstract:BACKGROUND:The association of CYP3A5, CYP3A4, and ABCB1 single nucleotide polymorphisms (SNPs) with cyclosporine (CsA) pharmacokinetics is controversial. The authors studied the influence of these SNPs on CsA pharmacokinetics as well as on the incidence of biopsy-proven acute rejection (BPAR) and renal function after k...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1097/FTD.0b013e31820feb8e
更新日期:2011-04-01 00:00:00
abstract::Central venous access catheters are commonly used in clinical oncology. The double lumen variant is applied in pharmacokinetic studies for simultaneous administration and blood sampling when frequent blood collections are necessary. Occlusion of one lumen, a common complication, necessitates the investigator perform b...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-200306000-00002
更新日期:2003-06-01 00:00:00
abstract::Pharmacokinetics of intravenous and oral pulsed high-dose dexamethasone were studied in four patients with pemphigus vulgaris. Doses for dexamethasone were varied from 100 to 300 mg. Serum concentrations were measured by high-performance liquid chromatographic procedure with diode assay detection. Bioavailability was ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/00007691-199910000-00007
更新日期:1999-10-01 00:00:00
abstract:BACKGROUND:Desmopressin (D-amino D-arginine vasopressin: dDAVP) is used for the treatment of patients with hemophilia A and Von Willebrand disease. Studies on the rationale of dosing are scarce and mainly focus on the underlying causes of the vast differences in desmopressin response among individuals. The aim of this ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/FTD.0000000000000791
更新日期:2020-12-01 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::The aims of this study were to determine the relationship between saliva and plasma methadone concentrations and the influence of variability in saliva pH. Saliva and plasma samples were taken before the daily dose of methadone in 60 patients undergoing methadone maintenance treatment (MMT). Saliva pH was measured imm...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章
doi:10.1097/01.ftd.0000164392.01779.db
更新日期:2005-10-01 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::Therapeutic drug monitoring (TDM) is commonly employed to optimize the dosing of certain drugs, including digoxin, aminoglycosides, theophylline, and phenytoin. Studies were reviewed in order to (a) evaluate the effect of TDM on the occurrence of toxic drug reactions (TDRs) and (b) identify factors that may modify or ...
journal_title:Therapeutic drug monitoring
pub_type: 杂志文章,meta分析
doi:10.1097/00007691-199001000-00013
更新日期:1990-01-01 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 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