Abstract:
BACKGROUND AND OBJECTIVE:Daclizumab high-yield process (DAC HYP) is a humanized monoclonal antibody that selectively blocks the α-subunit (CD25) of the high-affinity interleukin-2 receptors, and has shown robust efficacy as a treatment for multiple sclerosis (MS). This work quantitatively characterized the relationship between DAC HYP serum concentrations and saturation of CD25 expressed on antigen-rich target T cells in blood. METHODS:Serial pharmacokinetic and 968 CD25 measurements from three double-blind, randomized, placebo-controlled, phase I studies of DAC HYP (50-300 mg subcutaneous and 200-400 mg intravenous doses or placebo) in healthy volunteers (n = 95) were analyzed using nonlinear mixed-effects modeling. CD25 occupancy was determined using flow cytometry and a fluorescently-labeled DAC HYP-competing antibody. RESULTS:CD25 occupancy was described using a direct inhibitory sigmoidal maximum effect (E max) model (where DAC HYP fully inhibited CD25 labeling with competing antibody). Two IC50 (serum concentration corresponding to 50 % of maximal inhibition) parameters were used to describe rapid CD25 saturation at initiation of dosing and apparently slower desaturation during DAC HYP washout. Parameter estimates (95 % bootstrap confidence intervals) were: baseline CD25 labeling, 47 % (45-48); DAC HYP IC50(saturation), 0.023 µg/mL (0.005-0.073); IC50(desaturation) 0.86 µg/mL (0.74-0.98); Hill coefficient 5.6 (4.3-6.8). CONCLUSIONS:Based on the developed model, the 150 mg monthly subcutaneous regimen of DAC HYP in subjects with MS is predicted to saturate CD25 on target effector T cells within a few hours of dosing and maintain CD25 saturation during the entire dosing interval. Free CD25 levels return to baseline within 4-6 months of the last DAC HYP dose.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Minocha M,Tran JQ,Sheridan JP,Othman AAdoi
10.1007/s40262-015-0305-zsubject
Has Abstractpub_date
2016-01-01 00:00:00pages
121-30issue
1eissn
0312-5963issn
1179-1926pii
10.1007/s40262-015-0305-zjournal_volume
55pub_type
杂志文章,随机对照试验abstract::The safety profile of any pharmacological agent is defined on the basis of its toxicity, tolerability and potential for pharmacokinetic and/or pharmacodynamic interactions with other compounds, which may belong to the same or to a different pharmacological class. Drug-drug interactions are important in clinical practi...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199835020-00003
更新日期:1998-08-01 00:00:00
abstract::High dosage busulfan (1 mg/kg orally every 6 hours x 16 doses) is frequently used in preparative regimens for haemopoietic stem cell transplantation (HSCT). Busulfan is well absorbed after oral administration, exhibits low protein binding and is metabolised through conjugation with glutathione to form a thiophenium io...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200039020-00005
更新日期:2000-08-01 00:00:00
abstract::The US Food and Drug Administration (FDA) draft guidance for industry on drug interaction studies recommends, but does not mandate, that both cigarette smokers and non-smokers can be used to study drug metabolism in clinical trials, and that important results related to smoking should be included in drug labelling to ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-015-0246-6
更新日期:2015-05-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Veliparib (ABT-888) is a potent oral inhibitor of Poly(ADP-ribose) polymerase enzyme that is currently in development for the treatment of non-hematologic and hematologic malignancies. This analysis characterizes the population pharmacokinetics of veliparib, including developing a structural ph...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s40262-013-0130-1
更新日期:2014-05-01 00:00:00
abstract::The pharmacokinetic effect of extracorporeal elimination can be evaluated from the extracorporeal elimination rate constant, from the amount of drug removed, and from extracorporeal clearance. To compare the validity of these approaches in clinical practice, the effect of multiple plasma exchanges on the steady-state ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198510060-00004
更新日期:1985-11-01 00:00:00
abstract::The effects of anaesthesia and surgery on the pharmacokinetics of ketobemidone were studied in 12 patients. Plasma ketobemidone concentrations were assayed with a mass-fragmentographic method. The peroperative Vd(area) was 5.9 +/- 2.6L/kg and the terminal half-life was 3.9 +/- 1.7 h. In the postoperative period Vd(are...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198207030-00005
更新日期:1982-05-01 00:00:00
abstract::Few of the articles published on antibiotics and pregnancy are concerned with pharmacokinetics. It is particularly difficult to evaluate possible alterations in pharmacokinetic parameters that may be due to pregnancy. Most data available have been obtained in connection with abortion or delivery. Such data may not be ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-197904040-00003
更新日期:1979-07-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:This analysis used a population pharmacokinetic approach to identify covariates that influence plasma exposure of liraglutide 3.0 mg, a glucagon-like peptide-1 (GLP-1) receptor agonist approved for weight management in overweight and obese individuals. METHODS:Samples for pharmacokinetic anal...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40262-016-0410-7
更新日期:2016-11-01 00:00:00
abstract::The ability to deliver safe and effective moderate sedation is crucial to the ability to perform invasive procedures. Sedative drugs should have a quick onset of action, provide rapid and clear-headed recovery, and be easy to administer and monitor. A number of drugs have been demonstrated to provide effective sedatio...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200645090-00001
更新日期:2006-01-01 00:00:00
abstract::Despite progress in the treatment of metastatic colorectal cancer (mCRC) in the last 15 years, it is still a condition with a relatively low 5-year survival rate. Panitumumab, a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFR), is able to prolong survival in patients with mC...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-017-0590-9
更新日期:2018-04-01 00:00:00
abstract:OBJECTIVE:To assess the pharmacokinetic and pharmacodynamic behaviour of moxifloxacin in 15 consecutive elderly patients with acute exacerbation of chronic bronchitis (AECB) treated with the fixed oral moxifloxacin 400 mg/day regimen with the intent of verifying which degree of exposure may be ensured by this standard ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-200645030-00004
更新日期:2006-01-01 00:00:00
abstract::Low-molecular-weight heparins are anticoagulants used in the treatment of thrombosis. They have effectiveness and safety profiles similar to those of unfractionated heparin but are considered an attractive alternative because of their predictable pharmacokinetic characteristics. In this article, we demonstrate the nee...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/11532960-000000000-00000
更新日期:2010-09-01 00:00:00
abstract:BACKGROUND:A population pharmacokinetic (PK) protein-binding model was developed to (1) predict free mycophenolic acid (fMPA) based on total MPA (tMPA) concentrations in renal transplant patients, to establish the therapeutic range of fMPA through pharmacokinetic-pharmacodynamic studies; and (2) provide a guideline for...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-017-0603-8
更新日期:2018-07-01 00:00:00
abstract::Pegfilgrastim is a sustained-duration form of filgrastim, a recombinant methionyl form of human granulocyte colony-stimulating factor (G-CSF), to which a 20 kDa polyethylene glycol molecule is covalently bound to the N-terminal methionine residue. Similar to filgrastim, pegfilgrastim increases the proliferation and d...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/11586040-000000000-00000
更新日期:2011-05-01 00:00:00
abstract::The use of salicylates in rheumatic diseases has been established for over 100 years. The more recent recognition of their modification of platelet and endothelial cell function has lead to their use in other areas of medicine. Aspirin (acetylsalicylic acid) is still the most commonly used salicylate. After oral admin...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198510020-00004
更新日期:1985-03-01 00:00:00
abstract::Alemtuzumab is a humanized monoclonal antibody against CD52 and causes depletion of T and B lymphocytes, monocytes, and NK cells. Alemtuzumab is registered for the treatment of multiple sclerosis (MS) and is also used in chronic lymphocytic leukemia (CLL). Alemtuzumab is used off-label in kidney transplantation as ind...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-017-0573-x
更新日期:2018-02-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Elagolix is an oral, non-peptide, gonadotropin-releasing hormone receptor antagonist. It is approved for the treatment of moderate-to-severe pain associated with endometriosis and is being investigated for the treatment of heavy menstrual bleeding associated with uterine fibroids. Use of low-do...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-020-00921-y
更新日期:2021-01-01 00:00:00
abstract::Rapid drug delivery (arterial "boli') and high drug concentrations occur with nicotine inhaled in smoke. These are believed to be key elements in producing addiction to cigarettes. Preparations which reduce the rate of delivery and/or concentration of nicotine have been introduced as treatments for smoking cessation. ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199631010-00005
更新日期:1996-07-01 00:00:00
abstract::Carboplatin shares some of the therapeutic advantages of cisplatin, but without a significant incidence of the dose-limiting neurotoxicity and nephrotoxicity which is experienced with cisplatin. However, its use is associated with dose-limiting bone marrow suppression. Carboplatin is present in the blood as 3 distinct...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199733030-00002
更新日期:1997-09-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Currently, the majority of the surgical procedures performed in paediatric hospitals are done on a day care basis, with post-operative pain being managed by caregivers at home. Pain after discharge of these post-operative children has historically been managed with oral codeine in combination ...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s40262-015-0256-4
更新日期:2015-10-01 00:00:00
abstract::There are considerable laboratory data and information from animal and continuous culture in vitro models to support continuous infusion therapy for penicillins and cephalosporins, but, as yet, the only existing clinical data relate to cephalosporins. Penicillins do not exert concentration-dependent killing in the the...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199835050-00004
更新日期:1998-11-01 00:00:00
abstract::Obesity is associated with physiological changes that can alter the pharmacokinetic parameters of many drugs. Vancomycin and the aminoglycosides are the only antibacterials that have been extensively investigated in the obese population. The apparent volume of distribution (Vd) and total body clearance of vancomycin a...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200038050-00003
更新日期:2000-05-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Genetic polymorphisms of cytochrome P450 (CYP) 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) and patient demographic characteristics are responsible for inter-individual differences in warfarin maintenance dosage requirements. At present, however, the factors associate...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40262-012-0009-6
更新日期:2012-12-01 00:00:00
abstract::Thienopyridines are inactive prodrugs that are converted in vivo to active metabolites, which irreversibly bind to and inactivate platelet P2Y(12) receptors, and inhibit platelet activation and aggregation. Prasugrel is a third-generation thienopyridine, recently approved for prevention of thrombotic cardiovascular co...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/11537820-000000000-00000
更新日期:2010-12-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Therapeutic hypothermia can influence the pharmacokinetics and pharmacodynamics of drugs, the discipline which is called thermopharmacology. We studied the effect of therapeutic hypothermia on the pharmacokinetics of phenobarbital in asphyxiated neonates, and the clinical efficacy and the effe...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章
doi:10.1007/s40262-012-0004-y
更新日期:2012-10-01 00:00:00
abstract:OBJECTIVE:To investigate the effect of concomitant administration of dairy products on the pharmacokinetics and tolerability of moxifloxacin. DESIGN:This was a single-centre, randomised, controlled, nonblinded, 2-way crossover study in healthy volunteers. PARTICIPANTS:12 healthy men (aged 25 to 46 years) were enrolle...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-200140001-00005
更新日期:2001-01-01 00:00:00
abstract::Vedolizumab is a humanized anti-α4β7 integrin monoclonal antibody that selectively blocks trafficking of memory T cells to inflamed gut tissue by inhibiting the α4β7-mucosal addressin cell adhesion molecule-1 (MAdCAM-1) interaction. Approved for treating patients with moderately to severely active ulcerative colitis (...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-017-0546-0
更新日期:2017-11-01 00:00:00
abstract::The half-life of a drug, which expresses a change in concentration in units of time, is perhaps the most easily understood pharmacokinetic parameter and provides a succinct description of many concentration-time profiles. The calculation of a half-life implies a linear, first-order, time-invariant process. No drug per...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-200140040-00001
更新日期:2001-01-01 00:00:00
abstract:: ...
journal_title:Clinical pharmacokinetics
pub_type: 评论,信件
doi:10.1007/s40262-018-0665-2
更新日期:2018-07-01 00:00:00
abstract::The importance of in-depth knowledge about the pharmacokinetics of a drug is evident because pharmacokinetic behaviour may correlate with activity and toxicity. The most elaborate pharmacokinetic investigation is a so-called mass balance study employing a radioactive tracer. A mass balance study investigates the plasm...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200645010-00003
更新日期:2006-01-01 00:00:00