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 clinical pharmacology studies in which marketed solid formulations were administered. Based on a population pharmacokinetic model, mean concentration-time profiles were generated by varying the absorption rate constant and lag time. Subsequently, the simulated profiles were evaluated in a disease model of migraine to predict the onset and duration of the effect (the pain-free, pain-relief response). RESULTS:Based on a therapeutic dose of 50 mg of sumatriptan, a maximum gain in the pain-free response of 12% was achieved with an increased absorption rate. This gain in the response was reached approximately 0.5 hours after administration. A decrease only in the lag time with respect to the currently available formulations (i.e. 0.24 hours) resulted in a maximum gain of 5% in the pain-free response, which in contrast may not be interpreted as clinically relevant. CONCLUSION:Model-based predictions suggest that increases in the absorption rate of the currently marketed oral formulation of sumatriptan result in a gain in the pain-free response that is both clinically and statistically relevant.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Maas HJ,Spruit MA,Danhof M,Della Pasqua OEdoi
10.2165/00003088-200847020-00007subject
Has Abstractpub_date
2008-01-01 00:00:00pages
139-46issue
2eissn
0312-5963issn
1179-1926pii
4727journal_volume
47pub_type
杂志文章abstract:BACKGROUND AND OBJECTIVE:Febuxostat is a xanthine oxidase inhibitor indicated for gout and hyperuricemia. This work investigates potential clinically relevant covariates for febuxostat pharmacokinetics with a special focus on Asian race and bodyweight. METHODS:Febuxostat plasma concentrations from 141 male subjects we...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-020-00943-6
更新日期:2020-09-19 00:00:00
abstract::Hydroxymetabolites of the antidepressants nortriptyline and desipramine, like the parent drugs, inhibit neuronal uptake of noradrenaline (norepinephrine). In both plasma and cerebrospinal fluid (CSF), the concentrations of the 10-hydroxymetabolites of nortriptyline (10-OH-NT) are usually higher than those of the paren...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199528010-00004
更新日期:1995-01-01 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:BACKGROUND:Ovarian cancer is the leading cause of gynaecological cancer-related death in Western countries. Intraperitoneal (IP) peroperative chemotherapy is an interesting therapeutic option. However, very few data are available regarding pharmacokinetics and especially population pharmacokinetics. PATIENTS AND METHO...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-200948030-00003
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:NXY-059 (disufenton sodium, Cerovive, a nitrone with neuroprotective and free radical trapping properties (in experimental stroke) is under development for the treatment of acute stroke. The objectives of this study were to develop a population pharmacokinetic model for NXY-059 in acute stroke...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.2165/00003088-200544080-00007
更新日期:2005-01-01 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:BACKGROUND:Because of the vulnerability and frailty of elderly adults, clinical drug development has traditionally been biased towards young and middle-aged adults. Recent efforts have begun to incorporate data from paediatric investigations. Nevertheless, the elderly often remain underrepresented in clinical trials, e...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-016-0422-3
更新日期:2016-12-01 00:00:00
abstract:OBJECTIVE:To assess the dose proportionality of lacidipine after single and repeated oral doses, and to obtain new information on the pharmacokinetics of the compound since improvement of the plasma assay method. DESIGN:Open, randomised, four-way cross-over trial. PARTICIPANTS:24 healthy male and female volunteers, a...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-200342010-00004
更新日期:2003-01-01 00:00:00
abstract:BACKGROUND:Peripherally acting opioids, particularly peripheral κ-opioid agonists, may be effective for treating visceral pain by activating receptors expressed on afferent nerves within the gut. OBJECTIVE:The objective of this study was to investigate the pharmacokinetic/pharmacodynamic profile of a novel peripherall...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s40262-012-0023-8
更新日期:2013-02-01 00:00:00
abstract::Antibiotic therapy is one of the main treatments for cystic fibrosis (CF). It aims to eradicate bacteria during early infection, calms down the inflammatory process, and leads to symptom resolution of pulmonary exacerbations. CF can modify both the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of antibiotics,...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-020-00981-0
更新日期:2021-01-24 00:00:00
abstract:INTRODUCTION:Renal impairment may have a significant impact on the pharmacokinetics of drugs. Ad hoc studies in subjects with renal impairment are required by the regulatory authorities to propose dose adjustments in these subjects, to find a dosing regimen able to provide a systemic exposure similar to those in subjec...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-017-0574-9
更新日期:2018-04-01 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::Cyclosporin is a powerful immunosuppressive drug used in transplantation medicine and to treat autoimmune diseases. It is a lipophilic molecule, with its bioavailability dependent on food, bile and other interacting factors. Cyclosporin is extensively metabolised in the liver by the cytochrome P450 3A system, which is...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199324060-00004
更新日期:1993-06-01 00:00:00
abstract::The combination of hepatic artery infusion (HAI) of irinotecan, 5-fluorouracil and oxaliplatin with intravenous cetuximab has safely achieved prolonged survival in colorectal cancer patients with extensive liver metastases and prior treatment. Systemic exposure to the drugs or their main metabolites was determined dur...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s40262-016-0431-2
更新日期:2017-02-01 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:OBJECTIVE:To analyse the influence of covariates on the apparent clearance (CL) of tacrolimus in paediatric liver transplant recipients being converted from cyclosporin to tacrolimus. DESIGN:Retrospective modelling study. PATIENTS AND PARTICIPANTS:18 children, 13 girls and 5 boys, aged 4 months to 16 years (median 9....
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-200140010-00005
更新日期:2001-01-01 00:00:00
abstract::The hypolipidaemic agent pravastatin differs from other US Food and Drug Administration (FDA)-approved HMG-CoA reductase inhibitors (e.g. lovastatin and simvastatin) because it has greater hydrophilicity, as a result of the hydroxyl group attached to its decalin ring. The hydrophilic nature of pravastatin accounts for...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199427020-00002
更新日期:1994-08-01 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::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::Adequate immunosuppression minimising the risk of organ rejection with acceptable tolerability of the used drugs is a crucial step in organ transplantation. The primary goal is to maintain a consistent time-dependent target concentration by tailoring individual dosage leading to the best efficacy and tolerability comb...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200241050-00001
更新日期:2002-01-01 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
pub_type: 杂志文章
doi:10.1007/s40262-013-0089-y
更新日期:2013-12-01 00:00:00
abstract::Dorzolamide is a carbonic anhydrase inhibitor for topical ophthalmic application. It is used in the treatment of glaucoma to lower the intraocular pressure. After absorption via the cornea and stroma, it inhibits carbonic anhydrase in the ciliary process, which leads to a reduction of aqueous humour production and the...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200241030-00004
更新日期:2002-01-01 00:00:00
abstract::Clinical pharmacokinetics emerged as a clinical discipline in the late 1960s and early 1970s. Clinical pharmacokinetic monitoring (CPM) helped many pharmacists to enter the clinical arena, but the focus was more on the pharmacists and tools. With the widespread acceptance of pharmaceutical care and patient-focused pha...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199834040-00001
更新日期:1998-04-01 00:00:00
abstract::Following administration of equivalent oral doses (30mg) of either prednisone or prednisolone to 5 patients with chronic active liver disease who had failed to respond to therapy, 5 patients with chronic active liver disease in remission induced by prednisone, and 7 healthy volunteers, corticosteroid concentrations we...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198207050-00005
更新日期:1982-09-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:The likelihood of detecting a therapeutic signal of an effective drug for schizophrenia is impeded by a high placebo effect and by high dropout of patients. Several unsuccessful trials of schizophrenia, at least partly due to highly variable placebo effects, have indicated the necessity for a ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/11598460-000000000-00000
更新日期:2012-04-01 00:00:00
abstract::Inhibitors of sodium-glucose cotransporters type 2 (SGLT2) reduce hyperglycaemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. They are proposed as a novel approach for the management of type 2 diabetes mellitus. They have proven their efficacy in reducing glycated haemoglobin...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.1007/s40262-013-0128-8
更新日期:2014-04-01 00:00:00
abstract::The pharmacokinetics of dothiepin were evaluated in 9 depressed patients following a single oral dose of 75 mg. Blood and plasma concentrations of dothiepin and 2 major metabolites, northiaden and dothiepin S-oxide, were measured by gas chromatography/mass fragmentography. The mean (+/-SD) peak plasma concentrations o...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198308020-00004
更新日期:1983-03-01 00:00:00
abstract:OBJECTIVE:The objective of this study was to assess the pharmacokinetic and pharmacodynamic behavior of ticagrelor administered either as crushed (in the semi-upright sitting position) or as integral (in the supine position) tablets in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percu...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40262-015-0320-0
更新日期:2016-03-01 00:00:00
abstract::Measurement of drug levels is becoming increasingly popular to optimise the dosage of various drugs. In the case of antiarrhythmic drugs, the narrow therapeutic margin of most of these agents and a direct relationship between their pharmacological effects and plasma concentrations would justify more widespread use of ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198308010-00004
更新日期:1983-01-01 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