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 monitoring have identified potential markers that may have value in understanding calcineurin inhibitor pharmacodynamics. Integration of these markers has the potential to complement therapeutic drug monitoring. Existing pharmacokinetic-pharmacodynamic (PK-PD) data is largely limited to correlation between the biomarker and trough concentrations at single time points. Immune related gene expression currently has the most evidence supporting PK-PD integration. Novel biomarker-based approaches to pharmacodynamic monitoring including development of enhanced PK-PD models are proposed to realize the full clinical benefit.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Leino AD,Pai MPdoi
10.1007/s40262-020-00923-wsubject
Has Abstractpub_date
2020-11-01 00:00:00pages
1317-1334issue
11eissn
0312-5963issn
1179-1926pii
10.1007/s40262-020-00923-wjournal_volume
59pub_type
杂志文章,评审abstract::The pharmacokinetics of metoprolol have been studied in a group of patients with varying degrees of renal impairment and in healthy subjects after administration of 20 mg of metoprolol tartrate intravenously and 50 mg orally in a single dose and during steady-state conditions. There were no significant differences in ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198005020-00004
更新日期:1980-03-01 00:00:00
abstract::It should be recognized that children are not small adults, hence dosing in children should not be a 'small adult dose'. A mean population dose in all age groups is just an average dose and not necessarily the best or the correct dose for a given patient. The dose of a drug varies from patient to patient and individua...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-014-0134-5
更新日期:2014-04-01 00:00:00
abstract::Despite contributing significantly to the burden of global disease, the translation of new treatment strategies for diseases of the central nervous system (CNS) from animals to humans remains challenging, with a high attrition rate in the development of CNS drugs. The failure of clinical trials for CNS therapies can b...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-018-0632-y
更新日期:2018-09-01 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::Ertugliflozin, a selective inhibitor of sodium-glucose cotransporter 2 (SGLT2), is approved in the US, EU, and other regions for the treatment of adults with type 2 diabetes mellitus (T2DM). This review summarizes the ertugliflozin pharmacokinetic (PK) and pharmacodynamic data obtained during phase I clinical developm...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-020-00875-1
更新日期:2020-08-01 00:00:00
abstract::Necitumumab is a second-generation, recombinant, human immunoglobulin G1, epidermal growth factor (EGFR) receptor antibody that specifically blocks the ligand binding site of EGFR. Necitumumab potentially acts by blocking ligand epidermal growth factor (EGF) binding-mediated activation of the EGFR signaling pathway, i...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-016-0452-x
更新日期:2017-05-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:A simple approach is proposed to predict drug clearance in children when no paediatric data are available for drugs metabolised by cytochromes. METHODS:The maturation functions of cytochrome activity and binding proteins in plasma were combined with several measures of body size to describe dr...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-017-0596-3
更新日期:2018-07-01 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
pub_type: 杂志文章
doi:10.2165/00003088-200140060-00006
更新日期:2001-01-01 00:00:00
abstract::The alignment of drug metabolism and pharmacokinetic departments with drug discovery has not produced a radical improvement in the pharmacokinetic properties of new chemical entities. The reason for this is complex, reflecting in part the difficulty of combining potency, selectivity, water solubility, metabolic stabil...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200241130-00001
更新日期:2002-01-01 00:00:00
abstract::With the use of combination chemotherapy as well as a wide range of symptomatic therapies (e.g. analgesics and antiemetics) for the treatment of patients with cancer, the field of oncology practises polypharmacy to an extreme degree. The risk for a drug interaction under these conditions is high, and the pharmacologic...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198611030-00004
更新日期:1986-05-01 00:00:00
abstract::Ketoprofen, a potent nonsteroidal anti-inflammatory drug (NSAID) of the 2-arylpropionic acid class, has been used clinically for over 15 years in Europe, and has recently been introduced in the United States. Although it possesses a chiral centre, with only the S-enantiomer possessing beneficial pharmacological activi...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199019030-00004
更新日期:1990-09-01 00:00:00
abstract:OBJECTIVE:The objective of this analysis was to simulate the performance of oral triptan formulations with varying absorption characteristics and their impact on the onset and magnitude of the antimigraine effect using a Markov model for migraine attacks. ANALYSIS:Sumatriptan pharmacokinetic data were obtained from cl...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-200847020-00007
更新日期:2008-01-01 00:00:00
abstract:BACKGROUND:Fat-free mass (FFM)-based dose scaling is increasingly being adopted in clinical pharmacology. Given the complexities with the measurement of FFM in clinical practice, choosing an appropriate equation for FFM is critical for accurate dose scaling. Janmahasatian's FFM model (FFMJan) has largely remained the p...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-020-00883-1
更新日期:2020-09-01 00:00:00
abstract::5-Fluorouracil, first introduced as a rationally synthesized anticancer agent 30 years ago, continues to be widely used in the management of several common malignancies including cancer of the colon, breast and skin. This drug, an analogue of the naturally occurring pyrimidine uracil, is metabolised via the same metab...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198916040-00002
更新日期:1989-04-01 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:OBJECTIVE:To explore the ability of the nonparametric expectation maximisation (NPEM) method of population pharmacokinetic modelling to deal with sparse data in estimating systemic caffeine clearance for monitoring and evaluation of cytochrome P450 (CYP) 1A2 activity. DESIGN AND PARTICIPANTS:Nonblind, single-dose clin...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章
doi:10.2165/00003088-200342150-00006
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:Fondaparinux sodium is a novel antithrombotic agent, the first of a new class of selective factor Xa inhibitors. It has favourable pharmacokinetics including 100% bioavailability, low variability and a mean terminal half-life of 17 hours for young and 21 hours for elderly healthy volunteers, enabling once-da...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-200241002-00002
更新日期:2002-01-01 00:00:00
abstract::The results of research studies conducted to date in vitro and in healthy volunteers are practically all concordant in demonstrating the lack of any kind of interference between famotidine and microsomal oxidative metabolism. The pharmacokinetics (elimination half-life, area under the plasma concentration-time curve, ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-199324030-00006
更新日期:1993-03-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Preterm and term newborn infants show wide interindividual variability (IIV) in pharmacokinetic parameters of gentamicin. More extensive knowledge and use of predictive covariates could lead to faster attainment of therapeutic concentrations and a reduced need for concentration monitoring. This...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章
doi:10.2165/00003088-200948040-00003
更新日期:2009-01-01 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 OBJECTIVE:The use of an opportunistic (also called scavenged) sampling strategy in a prospective pharmacokinetic study combined with population pharmacokinetic modelling has been proposed as an alternative strategy to conventional methods for accomplishing pharmacokinetic studies in neonates. However, th...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-015-0291-1
更新日期:2015-12-01 00:00:00
abstract::Pharmacokinetic parameters of third generation cephalosporins vary widely, requiring different dosage regimens and adjustment methods for each agent. Although their antibacterial spectrum favours their usage in infections caused by aerobic Gram-negative organisms, due to their limited post-antibiotic effect against th...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199222020-00004
更新日期:1992-02-01 00:00:00
abstract::Intraventricular administration of chemotherapy is one approach to overcoming the limited distribution of anticancer drugs and their active metabolites into the CNS. This form of regional chemotherapy has led to effective treatment of occult and overt meningeal leukaemia in humans. In contrast, the efficacy of this th...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200544010-00001
更新日期:2005-01-01 00:00:00
abstract::There are many pathological changes in patients with cystic fibrosis (CF) which can lead to alterations in drug disposition. Although, in patients with CF, the extent of drug absorption varies widely and the rate of absorption is slower, bioavailability is not altered. Plasma protein binding for the majority of drugs ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199835040-00004
更新日期:1998-10-01 00:00:00
abstract::Clarithromycin is a semisynthetic macrolide antibiotic, structurally related to erythromycin. It has a more favourable pharmacokinetic profile than erythromycin, thus allowing twice-daily administration and possibly increasing compliance among outpatients. Clarithromycin is well absorbed from the gastrointestinal trac...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199325030-00003
更新日期:1993-09-01 00:00:00
abstract::Part I of this article, which appeared in the previous issue of the Journal, covered the following agents: histamine H2-receptor antagonists (cimetidine, ranitidine, famotidine, nizatidine); muscarinic-M1-receptor antagonists (pirenzepine); proton pump inhibitors (omeprazole); site-protective agents (colloidal bismuth...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199019020-00002
更新日期:1990-08-01 00:00:00
abstract::A substantial proportion of migraine patients have gastric stasis and suffer severe nausea and/or vomiting during their migraine attack. This may lead to erratic absorption from the gastrointestinal tract and make oral treatment unsatisfactory. For such patients, an intranasal formulation may be advantageous. Sumatrip...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200241110-00002
更新日期:2002-01-01 00:00:00
abstract::The treatment of epilepsy in pregnancy is particularly challenging in that the fetal and maternal risks associated with maternal seizures need to be balanced against the potential teratogenic effects of antiepileptic drugs (AEDs). Pregnancy is known to affect the pharmacokinetics of older-generation AEDs. Understandin...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200746030-00002
更新日期:2007-01-01 00:00:00
abstract::In the original publication, Page 3, Sect. 4.3, the first sentence was incorrectly published. ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,已发布勘误
doi:10.1007/s40262-018-0633-x
更新日期:2018-05-01 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