Abstract：
PURPOSES:Tacrolimus (TAC) is the most widely used immunosuppressant for the prevention of acute rejection after solid organ transplantation. Its pharmacokinetics (PK) show considerable variability, making TAC a good candidate for therapeutic drug monitoring (TDM). The principal aim of the study was to describe the PK of TAC in pediatric patients during the first year after transplantation. METHODS:Routine TDM trough levels of TAC were obtained from 42 pediatric liver allograft recipients during the first year after transplantation. A population PK model was developed using nonlinear mixed-effects modeling to describe TAC PK during this period and to explain the observed variability by means of patients' demographics, biochemical test results and physiological characteristics. RESULTS:The PK of TAC were best described by a two-compartment model with first-order elimination. Apparent volumes of the central compartment, intercomparmental clearance and maximum blood clearance estimates were 253 L, 115 L/day and 314 L/day, respectively. The absorption first-order rate and volume of peripheral compartment were fixed to 4.5 h(-1) and 100 L, respectively. While hematocrit levels, time after transplantation and bodyweight influenced TAC clearance, bodyweight was the only covariate retained on volume of distribution. CONCLUSIONS:We developed a TAC population PK model in pediatrics covering the first year after liver transplantation that may serve as a tool for TAC dose individualization as part of TDM.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Guy-Viterbo V,Scohy A,Verbeeck RK,Reding R,Wallemacq P,Musuamba FTdoi
10.1007/s00228-013-1501-0subject
Has Abstractpub_date
2013-08-01 00:00:00pages
1533-42issue
8eissn
0031-6970issn
1432-1041journal_volume
69pub_type
杂志文章abstract：:The influence of isosorbide dinitrate (ISDN) and food ingestion on superior mesenteric artery impedance was investigated in 24 healthy volunteers (age 40 +/- 2.7 years). Superior mesenteric artery circulation was assessed by duplex ultrasound. Pulsatility index (PI) was considered as a parameter of vascular resistance...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00196852
更新日期：1995-01-01 00:00:00
abstract：PURPOSE:To correct overdosing of drugs requiring adjustment based on renal function in intensive-care patients. METHODS:In a prospective intervention study, we estimated individual glomerular filtration rate and assessed whether medication required dose adjustment based on renal function. Senior clinicians received a ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-009-0643-6
更新日期：2009-08-01 00:00:00
abstract：:To assess the partial agonist activity of cicloprolol in man, four studies were carried out in normal male volunteers. I and II. Open dose escalating studies of the effects of oral doses of the drug on exercise tachycardia and sleeping heart rate. III and IV. Double-blind randomized studies of the effects of placebo, ...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00615219
更新日期：1988-01-01 00:00:00
abstract：OBJECTIVES:Designing a safe medication process requires the ability to model its reliability using methods such as probabilistic risk assessment (PRA). However, lack of data, especially on human-error probabilities (HEPs), limits its use. To assess whether small-scale simulations could help generate HEP data, a pilot s...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-007-0319-z
更新日期：2007-08-01 00:00:00
abstract：BACKGROUND:Many studies have indicated the adequate use of lipid-lowering drugs (LLDs) as a factor in reducing the risk of cardiovascular disease. However, in clinical practice, a very high percentage of patients are not adequately treated. OBJECTIVE:To analyze the management of hypercholesterolemia in a non-experimen...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-005-0911-z
更新日期：2005-05-01 00:00:00
abstract：:Intensive monitoring of adverse drug reactions (ADR) in infants and preschool children in the paediatric outpatient unit covering the town of Karlovac (150,000 inhabitants) was performed over a period of three months. Data were obtained by physical examination of children and the history given by their parents. In all...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00561025
更新日期：1989-01-01 00:00:00
abstract：:The kinetics of 14C-metformin have been studied in five healthy subjects after oral and intravenous administration. The intravenous dose was distributed to a small central compartment of 9.9 +/- 1.61 (X +/- SE), from which its elimination could be described using three-compartment open model. The elimination half-life...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00562061
更新日期：1979-09-01 00:00:00
abstract：:The pharmacokinetics of a single dose of netilmicin (NM) was studied in 6 healthy volunteers. Elimination of the drug was followed in serum and urine for 24 h and 72 h, respectively. NM concentrations were measured with a modified radioenzymatic assay. A three compartment open model was employed to calculate the pharm...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00605631
更新日期：1979-11-01 00:00:00
abstract：PURPOSE:The use of melatonin is increasing among Swedish children and adolescents despite deficient knowledge of usage in these groups. The aim of this study was to investigate the use of melatonin in Swedish children and adolescents according to age, gender, dosage, treatment duration, and use of attention deficit hyp...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-015-1866-3
更新日期：2015-07-01 00:00:00
abstract：:The pharmacokinetics, hypotensive effect and tolerability of a new vasodilator, tolmesoxide (T), have been studied in 6 uncontrolled hypertensive patients receiving atenolol and diuretic. After a 50 mg oral dose mean (+/- SD) peak plasma concentration of T was 1.13 +/- 0.29 micrograms/ml-1 and occurred 0.79 +/- 0.40 h...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00568397
更新日期：1981-01-01 00:00:00
abstract：PURPOSE:The purpose of this study is to determine the impacts of CYP3A5 polymorphism on tacrolimus concentration and the proportion of patients within a target therapeutic range during the first week after transplantation together with the 3-month acute rejection rate in kidney transplant patients receiving a minimized...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-015-1990-0
更新日期：2016-03-01 00:00:00
abstract：:Six children, aged 2 months - 4 years, received theophylline 5-6 mg/kg intravenously. Its disposition could be described by a two-compartment open model, the mean serum half life (t 1/2 beta) was 3.75 h, i.e., shorter than in adults, but there was a considerable interindividual variation (1.8-7.0 h, in one patient 13....
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00563120
更新日期：1979-09-01 00:00:00
abstract：PURPOSE:To develop a limited sampling strategy (LSS) to predict area under the concentration-time curve (AUC) ratios of omeprazole (AUC(OPZ)) to its metabolites 5-hydroxyomeprazole (AUC(5OH)) and omeprazole sulfone (AUC(SUL)) as phenotyping parameters for cytochrome P450 (CYP) 2C19 and 3A. METHODS:Data were obtained f...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s00228-011-1136-y
更新日期：2012-04-01 00:00:00
abstract：:Fifteen mild to moderate hypertensives were submitted to exercise testing using a bicycle ergometer with a fixed load. Heart rate, blood pressure and ECG were recorded throughout 5 min exercise and 10 min recovery. Oxygen uptake was measured during the final minute of exercise and blood glucose estimation and serum dr...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF00542508
更新日期：1983-01-01 00:00:00
abstract：:The pharmacodynamic effects of torasemide, a new potent loop diuretic, were compared with those of furosemide in a double blind controlled study in 18 hypertensive patients with oedema of various origins. Given orally for 5 days, torasemide was clinically very effective and well tolerated. On a weight basis, the diure...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00541464
更新日期：1986-01-01 00:00:00
abstract：OBJECTIVES:Caffeine-containing beverages are generally consumed by Nigerians suffering from malaria and kwashiorkor in the belief that caffeine aids early recovery from these illnesses, which are common in the tropics. However, there are no studies on the influence of these diseases on the absorption and pharmacokineti...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/s002280050734
更新日期：2000-05-01 00:00:00
abstract：PURPOSE:The quality of drug therapy is an important issue for nursing homes. This study aimed to assess the prevalence of polypharmacy and potentially inappropriate medications (PIMs) in a large sample of nursing home residents by using the data recorded during the preparation of pill dispensers. METHODS:This is a cro...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-016-2193-z
更新日期：2017-05-01 00:00:00
abstract：:A double blind crossover trial of baclofen against placebo in elderly stroke patients was discontinued because the drug produced an unacceptably high level of drowsiness. In a subsequent study baclofen 10 mg was given orally to 12 elderly stroke patients, and drug concentrations measured from a series of plasma sample...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00613463
更新日期：1985-01-01 00:00:00
abstract：:To evaluate the magnitude and duration of the antihypertensive effect of sustained release (SRO) isradipine, 37 uncomplicated essential hypertensive patients (diastolic blood pressure 100-115 mm Hg after a one month run-in on placebo) were randomised to receive, according to a double-blind cross-over design, isradipin...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00315275
更新日期：1993-01-01 00:00:00
abstract：AIMS:To determine whether the variability in cytochrome P(450) (CYP)3A4 metabolic function is exhibited at both transcription and translation levels and to examine the population distribution of CYP3A4 enzyme kinetics, protein, and mRNA. METHODS:Enzyme kinetics of testosterone 6beta-hydroxylation, immunoblot CYP3A4 pr...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-002-0487-9
更新日期：2002-08-01 00:00:00
abstract：OBJECTIVE:To evaluate the impact of the two most common CYP2C9 variant alleles (*2 and *3) on the maintenance dose of warfarin and on the quality of anticoagulation control in Brazilians. METHODS:Patients (n = 103) initiated warfarin therapy with 5 mg/day (or 2.5 mg/day when over 80 years old). The international norma...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-007-0385-2
更新日期：2008-01-01 00:00:00
abstract：:Tolbutamide (1 g/70 kg) was administered as a single intravenous dose to 31 healthy, non-smoking, drug-free males between 23 and 87 years old and the total amounts of hydroxy and carboxytolbutamide excreted in 24 h were measured. There was a significant decrease in the urinary recovery of both metabolites with age. Th...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF02336696
更新日期：1990-01-01 00:00:00
abstract：OBJECTIVE:The aim of the study was to determine the changes in consumption of psychotropic drugs by children aged less than 18 years during the years 1995 to 2001 in the Netherlands. METHODS:The year prevalence of antipsychotics, benzodiazepines, antidepressants and psychostimulants for boys and girls under 18 years w...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-004-0765-9
更新日期：2004-07-01 00:00:00
abstract：:The diabetogenic effect of deflazacort (DF), an oxazolinic synthetic corticosteroid, was studied in 12 healthy adult subjects with a positive family history of diabetes mellitus. Three oral glucose tests (oGTT) were performed at 9.00 a.m., after a 12 h fast, following randomized administration of Placebo (PL), or Defl...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00542555
更新日期：1982-01-01 00:00:00
abstract：PURPOSE:Nevirapine (NVP) is a non-nucleoside reverse transcriptase inhibitor, widely prescribed for type 1 human immunodeficiency virus infection. A small proportion of individuals treated with NVP experience severe cutaneous adverse events, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)....
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-013-1549-x
更新日期：2013-11-01 00:00:00
abstract：OBJECTIVE:Nafamostat mesilate, a potent protease inhibitor, is widely used for the treatment of pancreatitis, disseminated intravascular coagulation and as an anticoagulant in haemodialysis. However, hyperkalaemia associated with nafamostat mesilate has been reported. It is thought to be due to decreased urinary potass...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280050176
更新日期：1996-01-01 00:00:00
abstract：PURPOSE:To gain insight into the experiences and handling of adverse drug reactions (ADRs) by the staffs of public primary healthcare (PHC) clinics in Eastern Cape Province, South Africa, as well as their perceptions of related adherence challenges in the treatment and follow-up of human immunodeficiency virus (HIV)-po...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-012-1254-1
更新日期：2012-09-01 00:00:00
abstract：:Twenty-four healthy volunteers participated in a study on the disposition of ergotamine following oral and rectal administration. Plasma samples were collected surrounding each dose of medication and a new mass spectrometry method was used for quantitation of the samples. A mean peak plasma concentration of 454 pg/ml ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00541538
更新日期：1986-01-01 00:00:00
abstract：:Total beta-adrenoceptor density and beta 1- and beta 2-subtype distribution in right and left atria and in different ventricular regions from 14 failing and seven nonfailing human hearts have been compared. End-stage heart failure was due to idiopathic dilated cardiomyopathy (n = 8) or ischaemic cardiomyopathy (n = 6)...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00265923
更新日期：1992-01-01 00:00:00
abstract：OBJECTIVE:As quinine is mainly metabolised by human liver CYP3A4 and grapefruit juice inhibits CYP3A4, the effect of grapefruit juice on the pharmacokinetics of quinine following a single oral dose of 600 mg quinine sulphate was investigated. METHODS:The study was carried out in ten healthy volunteers using a randomis...
journal_title：European journal of clinical pharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/s002280050646
更新日期：1999-07-01 00:00:00
