Abstract:
:Since 1989 there has been an exponential introduction of new antiepileptic drugs (AEDs) into clinical practice and these include eslicarbazepine acetate, felbamate, gabapentin, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, perampanel, pregabalin, retigabine (ezogabine), rufinamide, stiripentol, tiagabine, topiramate, vigabatrin and zonisamide; 16 in total. Because often the treatment of epilepsy is lifelong, and because patients are commonly prescribed polytherapy with other AEDs, AED interactions are an important consideration in the treatment of epilepsy and indeed can be a major therapeutic challenge. For new AEDs, their propensity to interact is particularly important because inevitably they can only be prescribed, at least in the first instance, as adjunctive polytherapy. The present review details the pharmacokinetic and pharmacodynamic interactions that have been reported to occur with the new AEDs. Interaction study details are described, as necessary, so as to allow the reader to take a view as to the possible clinical significance of particular interactions. The principal pharmacokinetic interaction relates to hepatic enzyme induction or inhibition whilst pharmacodynamic interactions principally entail adverse effect synergism, although examples of anticonvulsant synergism also exist. Overall, the new AEDs are less interacting primarily because many are renally excreted or not hepatically metabolised (e.g. gabapentin, lacosamide, levetiracetam, topiramate, vigabatrin) and most do not (or minimally) induce or inhibit hepatic metabolism. A total of 139 pharmacokinetic interactions between concurrent AEDs have been described. The least pharmacokinetic interactions (n ≤ 5) are associated with gabapentin, lacosamide, tiagabine, vigabatrin and zonisamide, whilst lamotrigine (n = 17), felbamate (n = 15), oxcarbazepine (n = 14) and rufinamide (n = 13) are associated with the most. To date, felbamate, gabapentin, oxcarbazepine, perampanel, pregabalin, retigabine, rufinamide, stiripentol and zonisamide have not been associated with any pharmacodynamic interactions.
journal_name
Clin Pharmacokinetjournal_title
Clinical pharmacokineticsauthors
Patsalos PNdoi
10.1007/s40262-013-0087-0subject
Has Abstractpub_date
2013-11-01 00:00:00pages
927-66issue
11eissn
0312-5963issn
1179-1926journal_volume
52pub_type
杂志文章,评审abstract::There is a considerable range in the dose of many drugs that is required to produce a given pharmacological effect in an individual patient. This individual variation in dose requirement is sometimes reflected in the wide scatter in the steady state plasma concentration that follows the same oral dose of a drug given ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-197702010-00004
更新日期:1977-01-01 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::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 AND OBJECTIVES:Tesamorelin is a synthetic analogue of growth hormone-releasing factor (GRF), which increases basal and pulsatile growth hormone (GH) secretion and subsequently increases insulin-like growth factor (IGF)-1. Limited information is available about the pharmacokinetics of this compound. Consequen...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40262-014-0202-x
更新日期:2015-03-01 00:00:00
abstract::Rational pharmacotherapy is dependent upon an understanding of the clinical pharmacokinetic and pharmacodynamic properties of the drugs employed. Although the available data on drug biodisposition and action in the neonate have increased considerably in the last few years, pharmacokinetic-pharmacodynamic interactions ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198814040-00001
更新日期:1988-04-01 00:00:00
abstract::Nabumetone is a nonsteroidal anti-inflammatory drug (NSAID) of the 2,6-disubstituted naphthyl-alkanone class. Nabumetone is metabolised to an active metabolite 6-methoxy-2-napthylacetic acid (6-MNA) which is a relatively selective cyclo-oxygenase-2 inhibitor that has anti-inflammatory and analgesic properties. Nabumet...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199733060-00001
更新日期:1997-12-01 00:00:00
abstract:OBJECTIVE:The aim of these studies was to determine the absolute bioavailability in healthy volunteers of inhaled fluticasone propionate (FP) administered as a single dose via the Diskhaler and Diskus powder devices, and the pharmacokinetics of inhaled FP after repeated administration via the Diskhaler device. METHODS...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-200039001-00004
更新日期:2000-01-01 00:00:00
abstract:OBJECTIVE:Zanamivir, a clinically proven potent and specific inhibitor of influenza A and B neuraminidase, has been approved in some countries for the treatment of influenza and is in late-stage development for the prophylaxis of influenza. This study investigated whether the coadministration of zanamivir and influenza...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-199936001-00006
更新日期:1999-01-01 00:00:00
abstract::The influence of anaesthesia and surgery on the pharmacokinetics of pethidine (meperidine) was studied in 12 patients. Plasma pethidine concentrations in central venous blood collected during anaesthesia and the ensuing postoperative hours were by gas chromatography with electron capture detection. Postoperative analg...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198207020-00004
更新日期:1982-03-01 00:00:00
abstract::Models of tolerance are commonly derived on empirical grounds, because of lack of knowledge about the mechanism of tolerance or because of the difficulty of appropriately simplifying complex physiological processes. The present study was performed to evaluate the interchangeability of tolerance models used in the lite...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199936020-00005
更新日期:1999-02-01 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::The relative bioavailability of a single oral dose of temafloxacin given with and without enteral feeding was determined in 18 healthy male volunteers in a randomised crossover study. Subjects were administered 600mg of temafloxacin orally as an intact tablet, or a crushed tablet suspended in water administered throug...
journal_title:Clinical pharmacokinetics
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.2165/00003088-199200221-00008
更新日期:1992-01-01 00:00:00
abstract::Interleukins and tumour necrosis factor (TNF) are a complex group of proteins and glycoproteins able to exert pleiotropic effects with respect to a number of different target cells. In physiological conditions, they are induced and released in basal amounts only in restricted microenvironments where they have paracrin...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199121040-00004
更新日期:1991-10-01 00:00:00
abstract::Therapeutic drug monitoring is now widely used in many areas of medicine. With its proliferation has come an understanding of the clinical situations in which it is likely to be of value. Factors that can limit the usefulness of therapeutic drug monitoring and situations where it is less likely to be of benefit have a...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-198713040-00001
更新日期:1987-10-01 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::Escitalopram is the (S)-enantiomer of the racemic selective serotonin reuptake inhibitor antidepressant citalopram. Clinical studies have shown that escitalopram is effective and well tolerated in the treatment of depression and anxiety disorders. Following oral administration, escitalopram is rapidly absorbed and rea...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200746040-00002
更新日期:2007-01-01 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::25 patients with different degrees of chronic stable renal failure received oral treatment with cimetidine over 6 days and a final dose in the morning of day 7. The doses of cimetidine were reduced according to the degree of renal failure. Plasma concentrations of cimetidine were determined before the morning dose on ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-198106040-00006
更新日期:1981-07-01 00:00:00
abstract:BACKGROUND:Bitopertin (RG1678) is a glycine reuptake inhibitor currently in phase 3 trials for treatment of schizophrenia. This paper describes the use of physiologically based pharmacokinetic (PBPK) modelling and preclinical data to gain insights into and predict bitopertin clinical pharmacokinetics. METHODS:Simulati...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.1007/s40262-013-0061-x
更新日期:2013-08-01 00:00:00
abstract::Acute coronary syndromes (ACS) remain life-threatening disorders associated with high morbidity and mortality, despite advances in treatment over the last decade. Adenosine diphosphate-induced platelet activation via P2Y(12) receptors plays a pivotal role in the pathophysiology of ACS. The current standard of treatmen...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/11630960-000000000-00000
更新日期:2012-05-01 00:00:00
abstract::This article reviews the information available to assist pharmacokineticists in the prediction of metabolic drug interactions. Significant advances in this area have been made in the last decade, permitting the identification in early drug development of dominant cytochrome P450 (CYP) isoform(s) metabolising a particu...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-199732030-00004
更新日期:1997-03-01 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::Modifications to bodily functions and physiology are known to occur with age. These changes can have a considerable impact on the pharmacokinetic processes of absorption, distribution, metabolism and excretion and the pharmacodynamic properties of administered drugs. For many drugs with a high therapeutic index, this ...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200342140-00003
更新日期:2003-01-01 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
更新日期:1979-03-01 00:00:00
abstract::A change in drug clearance with age is considered an important factor in determining the high prevalence of adverse drug reactions associated with prescribing medications for the elderly. Despite this, no general principles have been available to guide drug administration in the elderly, although a substantial body of...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-199834050-00003
更新日期:1998-05-01 00:00:00
abstract:BACKGROUND:Febuxostat is a novel non-purine selective inhibitor of xanthine oxidase currently being developed for the management of hyperuricemia in patients with gout. OBJECTIVE:To investigate the pharmacokinetics, pharmacodynamics and safety of febuxostat over a range of oral doses in healthy subjects. METHODS:In a...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,随机对照试验
doi:10.2165/00003088-200645080-00005
更新日期:2006-01-01 00:00:00
abstract::The relation between steady-state plasma ethosuximide level and drug dose was studied in 46 patients. In this population, plasma drug levels were proportional to drug dose, expressed on a body weight basis. Age did not alter this relationship, but plasma levels increased more rapidly, relative to dose, in females than...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章
doi:10.2165/00003088-197904010-00004
更新日期:1979-01-01 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::Although activity of cytochrome P450 isoenzymes (CYPs) plays a major role in the fate of anticancer agents in patients, there are relatively few clinical studies that evaluate drug metabolism with therapeutic outcome. Nevertheless, many clinical reports in various non-oncology fields have shown the dramatic importance...
journal_title:Clinical pharmacokinetics
pub_type: 杂志文章,评审
doi:10.2165/00003088-200544040-00002
更新日期:2005-01-01 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