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 need for therapeutic monitoring of low-molecular-weight heparins by addressing evidence arising from the literature and from modelling and simulation. First, treatment targets for unfractionated heparin and enoxaparin sodium were identified. Then, 10 000 virtual patients were simulated and the rate of treatment success was calculated. Treatment success was found to be similar between the two drugs (48% with unfractionated heparin and 54% with enoxaparin sodium). These results are consistent with empirical evidence from the literature and reflect the inadequacy of current dosing strategies in achieving desired biomarker targets. These results, along with recent advances in Bayesian forecasting techniques, support the need for routine monitoring and dose individualization of enoxaparin sodium in order to improve treatment success.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Al-Sallami HS,Barras MA,Green B,Duffull SBdoi
10.2165/11532960-000000000-00000subject
Has Abstractpub_date
2010-09-01 00:00:00pages
567-71issue
9eissn
0312-5963issn
1179-1926pii
1journal_volume
49pub_type
杂志文章abstract::Leflunomide is the first disease-modifying antirheumatic drug to be approved for rheumatoid arthritis in the past 10 years. Orally administered leflunomide is almost completely converted into its active metabolite A77 1726 (hereafter referred to as M1). M1 displays linear pharmacokinetics at the dosages of leflunomide...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-200241060-00003
更新日期:2002-01-01 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:BACKGROUND:International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines emphasize the need for better understanding of the influence of ethnicity on drug response to minimize duplication of clinical studies, thereby expediting drug approval. OBJ...
journal_title:Clinical pharmacokinetics
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更新日期:2013-12-01 00:00:00
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journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-198611060-00006
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abstract::Bioequivalence of drug formulations plays an important role in drug development. Recently, the Biopharmaceutical Classification System (BCS) has been implemented for the purpose of waiving bioequivalence studies on the basis of the solubility and gastrointestinal permeability of drug substance. Using the rationale of ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200443150-00004
更新日期:2004-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Tegafur is an oral fluorouracil prodrug used in the treatment of colorectal cancer. The aim of this phase II, crossover, bioequivalence study was to compare the pharmacokinetics (primary objective) and tolerability (secondary objective) of tegafur-uracil (UFT) given as three daily doses (tid, r...
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更新日期:2007-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Two phase I drug interaction studies were performed with oral enzalutamide, which is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). METHODS:A parallel-treatment design (n = 41) was used to evaluate the effects of a strong cytochrome P450 (CYP) 2C8 inhib...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s40262-015-0283-1
更新日期:2015-10-01 00:00:00
abstract::Protein binding of antibacterials in plasma and tissues has long been considered a component of their pharmacokinetic parameters, playing a potential role in distribution, excretion and therapeutic effectiveness. Since the beginning of the 'antibacterial era', this factor has been extensively analysed for all antibact...
journal_title:Clinical pharmacokinetics
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doi:10.2165/00003088-200241100-00004
更新日期:2002-01-01 00:00:00
abstract::Pregnancy is a specific dynamic state, and the potential usefulness of caring for a disorder in the fetus or the mother is now well established. Previously, pregnant women have been excluded from clinical trials, therefore only a few studies concerning evaluation of the pregestational metabolism or transplacental tran...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199528020-00006
更新日期:1995-02-01 00:00:00
abstract::The intracellular pharmacokinetics of the different classes of antimicrobials into surrogate markers of tissue accumulation (alveolar macrophages and/or total alveolar cells collected by means of bronchoalveolar lavage or peripheral white blood cells) was reviewed. The aim of this review was to discuss the clinical im...
journal_title:Clinical pharmacokinetics
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doi:10.1007/s40262-017-0572-y
更新日期:2018-02-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Metformin is a biguanide used in the treatment of type 2 diabetes mellitus. In girls with a low birth weight, and early-normal and rapidly progressive puberty, metformin therapy is capable of modifying this outcome, prolonging pubertal growth, increasing height gain, delaying the age at menarch...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章
doi:10.2165/11593970-000000000-00000
更新日期:2011-11-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Daclatasvir is a potent, pangenotypic once-daily hepatitis C virus (HCV) NS5A inhibitor that is approved for the treatment of chronic HCV infection. The objective of this analysis was to characterize the pharmacokinetics of daclatasvir in subjects with chronic HCV infection. METHODS:A populati...
journal_title:Clinical pharmacokinetics
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doi:10.1007/s40262-016-0504-2
更新日期:2017-10-01 00:00:00
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journal_title:Clinical pharmacokinetics
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doi:10.1007/s40262-013-0061-x
更新日期:2013-08-01 00:00:00
abstract::Beta-adrenoceptor antagonists are among the most commonly prescribed classes of drugs. They are indicated for the treatment of diseases such as hypertension and angina pectoris, in which long term therapy is often required. Since many beta-adrenoceptor antagonists have short plasma elimination half-lives, divided dail...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198713010-00003
更新日期:1987-07-01 00:00:00
abstract::The overall reporting rate of drug-drug interactions with fluvoxamine is very low: only 73 cases have been identified from an estimated exposure of over 8 million patients worldwide. The reporting rate is similar in men and women, and most events relate to the use of fluvoxamine in conjunction with psychotropic compou...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199500291-00006
更新日期:1995-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Milrinone is the drug of choice for the treatment and prevention of low cardiac output syndrome (LCOS) in paediatric patients after open heart surgery across Europe. Discrepancies, however, among prescribing guidance, clinical studies and practice pattern require clarification to ensure safe an...
journal_title:Clinical pharmacokinetics
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doi:10.1007/s40262-013-0096-z
更新日期:2014-01-01 00:00:00
abstract::This review describes the pharmacokinetics of the major drugs used for the treatment of inflammatory bowel disease. This information can be helpful for the selection of a particular agent and offers guidance for effective and well tolerated regimens. The corticosteroids have a short elimination half-life (t1/2beta) of...
journal_title:Clinical pharmacokinetics
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doi:10.2165/00003088-200140100-00003
更新日期:2001-01-01 00:00:00
abstract::Mifepristone is a steroidal antiprogestin and antiglucocorticoid acting at the receptor level. The aromatic dimethylaminophenyl side chain in position 11 of the steroid structure is essential for the antagonistic properties of mifepristone. The pharmacokinetics of mifepristone are characterised by rapid absorption, a ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-199733010-00002
更新日期:1997-07-01 00:00:00
abstract:OBJECTIVE:To obtain a pharmacokinetic profile of cyclosporin microemulsion formulation in patients with inflammatory bowel disease. PATIENTS AND PARTICIPANTS:58 consecutive patients (19 women and 39 men), aged 16 to 64 years (mean age 38 years), with a diagnosis of ulcerative colitis (29 patients) or Crohn's disease (...
journal_title:Clinical pharmacokinetics
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doi:10.2165/00003088-200140060-00006
更新日期:2001-01-01 00:00:00
abstract::20 routine patients with endogenous depression were investigated in a kinetic and 4 week treatment study. Steady-state plasma nortriptyline concentrations above 200 microgram/L were associated with a highly significant poorer therapeutic outcome. The correlations between the 24, 48 and 72 hour concentrations and stead...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章
doi:10.2165/00003088-197904020-00005
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journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199121010-00003
更新日期:1991-07-01 00:00:00
abstract::The pharmacokinetics of gentamicin were studied after total hip joint arthroplasties in 2 groups of 10 patients. The prosthesis was performed in the first group with 'Palacos R plus gentamicin' (normal viscosity), manufactured by Schering, and in the second group with 'Cerafix genta R' (low viscosity) manufactured by ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-199019040-00005
更新日期:1990-10-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:The aim of this study was to investigate the pharmacokinetics, safety, and tolerability of riociguat after single and multiple oral doses of 1 or 2 mg three times daily (tid), and to determine the effect of smoking on riociguat pharmacokinetics in Chinese men. METHODS:In a randomized, double-...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40262-015-0337-4
更新日期:2016-05-01 00:00:00
abstract::Calcineurin inhibitors, the primary immunosuppressive therapy used to prevent alloreactivity of transplanted organs, have a narrow therapeutic index. Currently, treatment is individualized based on clinical assessment of the risk of rejection or toxicity guided by trough concentration monitoring. Advances in immune mo...
journal_title:Clinical pharmacokinetics
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更新日期:2020-11-01 00:00:00
abstract:BACKGROUND:Entecavir is an orally administered guanosine nucleoside analog with activity against hepatitis B virus (HBV) polymerase, which is approved for the treatment of chronic hepatitis B (CHB) infection in adults and children ≥2 years old (USA and EU). OBJECTIVE:To develop simplified entecavir dosing recommendati...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-016-0420-5
更新日期:2016-12-01 00:00:00
abstract::Inadequate pain control in the postoperative period not only contributes to patient discomfort, but also causes physiological changes that may result in increased risk of myocardial ischaemia, deep vein thrombosis and pulmonary embolism. These events complicate postoperative recovery and may lead to longer hospital st...
journal_title:Clinical pharmacokinetics
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doi:10.2165/00003088-200544001-00002
更新日期:2005-01-01 00:00:00
abstract::Fluvoxamine is a selective inhibitor of serotonin reuptake that is widely used in the management of depression. Following oral administration, the drug is absorbed efficiently from the gastrointestinal tract. Peak plasma concentrations are usually observed within 2 to 8 hours postdose for capsules and film-coated tabl...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199427030-00002
更新日期:1994-09-01 00:00:00
abstract::Interpatient pharmacokinetic variability normally observed in adults is often of even greater magnitude in paediatric patients because of age-related maturation of physiological processes responsible for drug disposition. Several antineoplastic agents have shown age-related changes, including alterations in volume of ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198712030-00002
更新日期:1987-03-01 00:00:00
abstract::Most of the currently available psychotropic drugs form 1 or more active metabolites during in vivo biotransformation in humans and/or animals. In some cases these metabolites are rapidly conjugated and excreted, but in others they attain blood and/or brain concentrations within the same range as, or even higher than,...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199018060-00002
更新日期:1990-06-01 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
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doi:10.2165/11586040-000000000-00000
更新日期:2011-05-01 00:00:00