Abstract:
:All of the commonly used anticonvulsants drugs, except possibly primidone, are cleared from the human body mainly by metabolism. The metabolites of phenytoin, phenobarbital and ethosuximide have so far not been shown to possess significant pharmacological activity. However, carbamazepine-10,11-epoxide, derived from carbamazepine, has anticonvulsant activity comparable with that of its progenitor, while oxcarbazepine, a new anticonvulsant congener of carbamazepine, is essentially a prodrug for its 10-hydroxy derivative. Valproic acid forms numerous metabolites through a variety of pathways; 2-en valproic acid, a beta-oxidation derivative, probably contributes to its anticonvulsant action, though the extent of the contribution is uncertain. Another metabolite, 4-en-valproic acid, has been considered a possible hepatotoxin and teratogen. N-Methyl-phenobarbital and primidone, though both anticonvulsants in their own right, are metabolised to phenobarbital, which probably mediates much of their antiseizure effect. Primidone also yields the weaker anticonvulsant phenylethylmalonamide. The various benzodiazepine anticonvulsants form numerous metabolites, some of which possess both antiseizure and other forms of pharmacological activity. As yet, there is little understanding of how best to interpret simultaneous plasma concentration measurements of anticonvulsant drug and its active metabolite (or metabolites) in the clinical situation, and the possible roles of anticonvulsant metabolites in the idiosyncratic toxicity of these drugs remain largely unexplored.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Eadie MJdoi
10.2165/00003088-199121010-00003subject
Has Abstractpub_date
1991-07-01 00:00:00pages
27-41issue
1eissn
0312-5963issn
1179-1926journal_volume
21pub_type
杂志文章,评审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::Fluorouracil is used clinically against various solid tumours. Both fluorouracil toxicity and pharmacokinetics vary highly within and between individuals. The reasons why doses are not individualised routinely are difficulties in defining, predicting and achieving an optimal fluorouracil exposure or dose because of a ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200645060-00002
更新日期:2006-01-01 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::For the past 300 years antimalarial dosage regimens have not been based on pharmacokinetic information. However, now that this information is available, it is appropriate to examine current recommendations for prophylaxis and treatment. In healthy subjects, the cinchona alkaloids (quinine and quinidine), primaquine an...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198510030-00001
更新日期:1985-05-01 00:00:00
abstract::Dosage adjustments can be difficult and time-consuming, especially for the non-specialist. The objective of this investigation was to obtain shortcut formulae to calculate dosage adjustments for (i) a drug obeying linear pharmacokinetics (i.e. first order) and given orally, by a continuous infusion or by an intermitte...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/11313460-000000000-00000
更新日期:2009-01-01 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:OBJECTIVE:The aim of this study was to characterize the relationship between morphine plasma concentration and repeated time to postoperative remedication events in children undergoing cardiac surgery. METHODS:Data from our previously published study of morphine pharmacokinetics were utilized in this pharmacodynamic s...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-016-0398-z
更新日期:2016-10-01 00:00:00
abstract:BACKGROUND AND OBJECTIVE:Dosing of therapeutic monoclonal antibodies (mAbs) is often based on body size, with the perception that body size-based dosing would reduce inter-subject variability in drug exposure. However, most mAbs are target specific with a relatively large therapeutic window and generally a small contri...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/11596370-000000000-00000
更新日期:2012-02-01 00:00:00
abstract:BACKGROUND AND OBJECTIVES:Imeglimin (IMEG) is the first in a novel class of oral glucose-lowering agents with a unique mechanism of action targeting mitochondrial bioenergetics. We assessed whether repeated co-administration of IMEG and either metformin (MET) or sitagliptin (SITA) would influence the pharmacokinetics o...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.1007/s40262-020-00886-y
更新日期:2020-10-01 00:00:00
abstract::In the drug therapy of cardiac emergencies, it is necessary to rapidly achieve therapeutic drug concentrations and adjust drug dose as the patient's clinical status changes. Cardiac dysfunction is often present and may alter drug pharmacokinetics. Circulatory failure causes sympathetically mediated vasoconstriction in...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198409040-00001
更新日期:1984-07-01 00:00:00
abstract::Pancuronium is frequently used in coronary artery surgery, but its pharmacokinetics in these patients are still unknown. It is possible that dopamine, administered to prevent renal impairment induced by the surgery, might promote the elimination of pancuronium. Therefore, the pharmacokinetics of a bolus dose of pancur...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-199019060-00005
更新日期:1990-12-01 00:00:00
abstract::Although individualised antihypertensive therapy is widely recommended, prospective methods for optimising treatment are hampered by the paucity of basic information about dose-plasma concentration-response relationships for commonly used drugs. Concentration-effect analysis has been applied to a number of therapeutic...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199426060-00005
更新日期:1994-06-01 00:00:00
abstract::Warfarin, like all the 4-hydroxycoumarin compounds, has an asymmetric carbon atom. The clinically available warfarin preparations consist of a racemic mixture of equal amounts of 2 distinct S and R isomers, the former being 4-times more potent as anticoagulant and more susceptible to drug interaction. Warfarin is high...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199630040-00003
更新日期:1996-04-01 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::Morphine, morphine-6-glucuronide (M6G), morphine-3-glucuronide (M3G) and normorphine were analysed with high performance liquid chromatography in plasma and urine, collected over 72 h after administration of single intravenous 5 mg and oral 20 mg doses of morphine to 7 healthy volunteers. Systemic plasma clearance of ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-199324040-00007
更新日期:1993-04-01 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::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:INTRODUCTION:Because the multimodal antidepressant vortioxetine is likely to be coadministered with other central nervous system (CNS)-active drugs, potential drug-drug interactions warrant examination. OBJECTIVE:These studies evaluated whether there are pharmacokinetic and/or pharmacodynamic interactions between vort...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40262-016-0389-0
更新日期:2016-09-01 00:00:00
abstract::Amiodarone is an iodinated benzofuran derivative with recognised antiarrhythmic activity in man. As yet, its pharmacokinetic behaviour has not been satisfactorily characterised. Specific and sensitive high-pressure liquid chromatographic methods have become available only recently and this partly explains the scarcity...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198409020-00002
更新日期:1984-03-01 00:00:00
abstract::Doxycycline and minocycline are second-generation tetracyclines. They are readily absorbed, distributed throughout the organism as a function of their lipophilicity and eliminated in both the urine and the faeces. The influence of age, renal disease, malnutrition and hyperlipidaemia is reviewed, together with the main...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198815060-00001
更新日期:1988-12-01 00:00:00
abstract::The ability of a new multiple-dose non-linear regression analysis program to predict steady-state aminoglycoside peak and trough serum concentrations was evaluated. 30 patients receiving either amikacin (7), gentamicin (10) or tobramycin (13) were studied. A standard method of prediction which requires the collection ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198308050-00006
更新日期:1983-09-01 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::This review examines the literature on drug interactions with omeprazole. Different mechanisms have been proposed as potential causes for such interactions. First, the absorption of some drugs might be altered due to the decreased intragastric acidity resulting from omeprazole treatment. There was no effect of omepraz...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199121030-00004
更新日期:1991-09-01 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::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
pub_type: 杂志文章
doi:10.2165/00003088-200140060-00006
更新日期:2001-01-01 00:00:00
abstract::Renewed interest in vancomycin over the past decade has led to an abundance of data concerning the pharmacokinetics of vancomycin, and its dosage selection and concentration-response relationships. No definitive data exist that correlate vancomycin serum concentrations with clinical outcomes. However, inconsistencies ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199528040-00005
更新日期:1995-04-01 00:00:00
abstract:BACKGROUND:Fast-acting insulin aspart (faster aspart) is an ultra-fast-acting formulation of insulin aspart (IAsp). This post hoc analysis investigated the pharmacokinetics of faster aspart versus IAsp, measured as free or total IAsp, and the relationship between anti-IAsp antibodies and the pharmacokinetics/pharmacody...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s40262-018-0718-6
更新日期:2019-05-01 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: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