Abstract：
PURPOSE:To investigate pharmacokinetics (PK) of encapsulated CPT-11, released CPT-11 and the active metabolite SN-38 following administration of IHL-305 and to identify factors that may influence IHL-305 PK. METHODS:Plasma samples from 39 patients with solid tumors were collected in a phase I study. IHL-305 was administered as a 1 h IV infusion with doses ranging from 3.5 to 210 mg/m(2). Plasma concentrations of encapsulated CPT-11, released CPT-11 and SN-38 were used to develop a population PK model using NONMEM®. RESULTS:PK of encapsulated CPT-11 was described by 1-compartment model with nonlinear clearance and PK of released CPT-11 was described by a 1-compartment model with linear clearance for all patients. PK of the active metabolite SN-38 was described by a 2-compartment model with linear clearance for all patients. Covariate analysis revealed that gender was a significant covariate for volume of distribution of encapsulated CPT-11. Vencap in male patients is 1.5-fold higher compared with female patients. CONCLUSIONS:The developed population PK modeling approach is useful to predict PK exposures of encapsulated and released drug and can be applied to the more than 300 other nanoparticle formulations of anticancer agents that are currently in development. The effect of gender on PK of IHL-305 needs to be further evaluated.
journal_name
Eur J Clin Pharmacoljournal_title
European journal of clinical pharmacologyauthors
Wu H,Infante JR,Keedy VL,Jones SF,Chan E,Bendell JC,Lee W,Zamboni BA,Ikeda S,Kodaira H,Rothenberg ML,Burris HA 3rd,Zamboni WCdoi
10.1007/s00228-013-1580-ysubject
Has Abstractpub_date
2013-12-01 00:00:00pages
2073-81issue
12eissn
0031-6970issn
1432-1041journal_volume
69pub_type
杂志文章abstract：:The study was done in healthy volunteers to investigate the vasoconstrictor activity of three commercially available formulations of fluocinolone acetonide (Synalar gel, cream and ointment) and to determine whether they were bioequivalent. The influence of dilution of the cream formulation on activity was also examine...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00195919
更新日期：1994-01-01 00:00:00
abstract：:Thirty-eight severely hypertensive patients were treated with oral clonidine. Each patient received a "loading" dose of 0.2 mg clonidine, followed by 0.1 mg hourly until the blood pressure was substantially reduced, or until a total dose of 0.8 mg has been administered. Thirty-five (82.1%) patients responded favourabl...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00606664
更新日期：1986-01-01 00:00:00
abstract：AIM:Mizoribine (MZR) is an immunosuppressant for the prevention of allograft rejection in Asian countries, but the great variability in pharmacokinetics (PK) limits its clinical use. This study was to explore genetic and clinical factors that affect the MZR PK process. METHODS:Blood samples and clinical data were coll...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-02936-7
更新日期：2021-01-01 00:00:00
abstract：OBJECTIVE:To investigate the drug interaction potential between itraconazole and nevirapine. METHODS:Our study was conducted in 12 healthy volunteers in two phases. In phase 1 (from days 1-28), all subjects were randomly assigned to a two-way crossover study of a nevirapine regimen (nevirapine 200 mg once daily for 7 ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,随机对照试验
doi：10.1007/s00228-007-0280-x
更新日期：2007-05-01 00:00:00
abstract：PURPOSE:The purpose of this study is to investigate the association between polypharmacy with health-related quality of life (HRQoL) and medication regimen complexity with HRQoL in residential aged care facilities (RACFs). METHODS:A cross-sectional study of 383 residents from six Australian RACFs was conducted. The pr...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-016-2075-4
更新日期：2016-09-01 00:00:00
abstract：:The interaction between isofezolac and probenecid has been studied with the aid of a specific HPLC assay for isofezolac in plasma and urine. 8 healthy adult volunteers received a single 40 mg oral dose of isofezolac before and after 3 days of loading with 0.5 probenecid t.i.d. There was an increase in the maximum plas...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00544363
更新日期：1985-01-01 00:00:00
abstract：OBJECTIVE:To analyse the contribution of adverse drug reactions (ADR) to hospital readmissions. METHODS:This was a case-control study in which unscheduled admissions of patients who had been admitted to the hospital during the two previous months were assessed during a 21-month period. The patient was considered a cas...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-008-0473-y
更新日期：2008-07-01 00:00:00
abstract：:The interaction between the main components of the new glycopeptide antibiotic teicoplanin, A2-2, A2-3, A2-4, A2-5 and A3-1, and human serum albumin has been studied in vitro by equilibrium dialysis (pH 7.4, 37 degrees C). From Scatchard analysis of the data, the calculated association constants (Ka) were: A2-2, 2.47 ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00544566
更新日期：1987-01-01 00:00:00
abstract：UNLABELLED:The steady-state pharmacokinetics of nefazodone (NEF) and its metabolites hydroxynefazodone (HO-NEF) and m-chlorophenylpiperazine (mCPP) were compared in subjects with normal and impaired renal function. PATIENTS:The Study was of parallel group design which included 7 subjects with normal (NOR) renal functi...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00192384
更新日期：1995-01-01 00:00:00
abstract：PURPOSE:Lithium (Li), the first-line treatment of bipolar disorder, was first developed as an immediate-release form with a routine therapeutic drug monitoring 12 h after the last dose. In Europe, the most commonly prescribed form is a sustained release (srLi). Yet no pharmacokinetics (PK) study has been published of s...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-018-2605-3
更新日期：2019-04-01 00:00:00
abstract：:Right ventricular repolarisation and refractoriness after therapeutic doses of disopyramide have been studied in 10 patients with coronary artery disease by recording monophasic action potentials (MAP) during programmed stimulation. Using 2 catheters, with the tip of one in the apex and the other in the outflow tract ...
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/BF00558240
更新日期：1988-01-01 00:00:00
abstract：PURPOSE:Treatment with statins requires close monitoring of serum creatine kinase (CK) levels to prevent myopathy, a common and potentially serious dose-dependent adverse effect of these drugs. We have investigated the correlation between elevated CK levels and polymorphisms in the genes encoding transporters involved ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-014-1661-6
更新日期：2014-05-01 00:00:00
abstract：:We have evaluated the pharmacokinetics of high doses of clonidine, as used in the prophylactic treatment of alcohol withdrawal syndrome, in 11 alcohol-dependent patients undergoing surgery for oesophagogastrectomy. Clonidine was given in a bolus of 150 micrograms followed by a continuous infusion. After a mean period ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00315500
更新日期：1993-01-01 00:00:00
abstract：PURPOSE:Serotonin receptor 1B (HTR1B) is involved in the regulation of the serotonin system, playing different roles in specific areas of the brain. We review the characteristics of the gene coding for HTR1B, its product and the functional role of HTR1B in the neural networks involved in motivation and memory; the cent...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00228-009-0724-6
更新日期：2010-01-01 00:00:00
abstract：:Cimetropium bromide is an antimuscarinic compound with antispasmodic properties. Its effect on meal-stimulated sigmoid motor activity in 30 patients with the irritable bowel syndrome, mainly with pain and constipation, has been evaluated. The mechanical activity of the sigmoid colon was recorded with a probe with thre...
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/BF00542489
更新日期：1988-01-01 00:00:00
abstract：:Factors which might affect paracetamol disposition have been studied in a heterogenous group of patients in need of mild analgesia in an intensive care unit. Following oral administration of 1 g of paracetamol, plasma and urinary concentrations of the parent compound and metabolites were assessed by HPLC. The renal cl...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00315104
更新日期：1990-01-01 00:00:00
abstract：AIMS:The study aimed to identify and describe adverse drug reactions and adherence to clinical guidelines in patients receiving treatment for type 2 diabetes mellitus (T2DM) in Cameroon. METHODS:The method used was a cross-sectional study at a tertiary diabetes care service in Yaoundé, Cameroon. Adult T2DM patients at...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-020-02949-2
更新日期：2020-11-01 00:00:00
abstract：:The number of marketed non-steroidal anti-inflammatory agents varies widely from one European country to another, partly as a consequence of differing regulatory policies. During a four-year period, nine of 18 applications to market such drugs in the Netherlands failed; the remaining nine compounds were all licenced; ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00558371
更新日期：1981-01-01 00:00:00
abstract：OBJECTIVES:Inhaled corticosteroids (ICS) are widely used in the treatment of asthma. We studied the suspected adverse drug reactions (sADRs) reported during the use of ICS in the Netherlands. METHODS:In the Netherlands, health professionals and patients can report suspected ADRs to the Pharmacovigilance Centre Lareb. ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-006-0102-6
更新日期：2006-05-01 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：: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 explore and compare the opinions of physicians, pharmacists and potential users on the readability of a package insert of an over-the-counter medicine. METHODS:Exploratory study based on the administration of a semi-open questionnaire. This instrument was developed according to the readability guideline of ...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-014-1645-6
更新日期：2014-05-01 00:00:00
abstract：OBJECTIVE:Psychotropic drug use among nursing home residents with regard to diagnostic indications and patient- and institution characteristics was analysed. METHODS:A cross-sectional study of medication data from 1552 residents at 23 nursing homes in Bergen, Norway, was performed. Psychotropic drug use (neuroleptics,...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280100348
更新日期：2001-09-01 00:00:00
abstract：OBJECTIVE:To investigate the potential for pharmacokinetic interactions between moexipril, a new converting enzyme inhibitor, and hydrochlorothiazide after single dose administration. METHODS:12 healthy male volunteers were studied by an open, randomised, three-way cross-over design, in which single doses of moexipril...
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/s002280050209
更新日期：1996-01-01 00:00:00
abstract：:The role of mental stress in the development of hypertension and coronary heart disease remains uncertain. Its effects are likely to depend on an interaction of at least three factors: the nature of the stressor, its perception by the individual, and the individual's physiological susceptibility. This type of interact...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：
更新日期：1990-01-01 00:00:00
abstract：:Clorazepate 20 mg was given i.m. to 49 mothers during the first stage of labour. The elimination of the drug was studied in 27 newborns produced by these mothers. The same dose was given to 13 women who underwent amniocentesis and to 7 women who were breast-feeding. "Total nordiazepam", i.e. the sum of clorazepate and...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00563103
更新日期：1979-04-17 00:00:00
abstract：PURPOSE:The continuous growth of antidepressant consumption and expenditure, especially for selective serotonin reuptake inhibitors (SSRIs), has led to the adoption of several policy measures directed toward cost control in Western countries. In Italy, copayment policies have been heterogeneously introduced at a region...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s00228-012-1422-3
更新日期：2013-04-01 00:00:00
abstract：:The immunosuppressive activity of azathioprine (AZA) is unpredictable and depends on the formation of intracellular thiopurine ribonucleotides. However, the quantification of these active thiopurines presents difficult analytical problems. It has recently been postulated that plasma concentrations of 6-thiouric acid (...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/BF00558158
更新日期：1989-01-01 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：BACKGROUND:Fexofenadine is the active metabolite of the non-sedating anti-histamine terfenadine. Pre-licensing clinical trials in over 6000 patients suggested it was effective and well tolerated. OBJECTIVE:To assess the tolerability and safety of fexofenadine immediately after its availability on the UK market in Marc...
journal_title：European journal of clinical pharmacology
pub_type： 杂志文章
doi：10.1007/s002280100292
更新日期：2001-07-01 00:00:00
