Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics

Sandor, Paul; Sellers, Edward M.; Dumbrell, M; Khouw, V

doi:10.1038/clpt.1981.178

Cited by 34 publications

(18 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The clearances of phenytoin, tolbutamide and warfarin, but not aminopyrine, have been reported to increase in hospitalised alcoholic subjects in the period following ethanol withdrawal [1537][1538][1539]. In chronic alcoholic subjects, the clearance of tolbutamide clearance was apparently more than 2-fold greater compared with the control group [1537].…”

Section: Drug-drug Interactions Owing To Induction Of Cyp2c9mentioning

confidence: 95%

Substrates, Inducers, Inhibitors and Structure-Activity Relationships of Human Cytochrome P450 2C9 and Implications in Drug Development

Zhou¹,

Zhou²,

Liu³

et al. 2009

CMC

149

View full text Add to dashboard Cite

Cytochrome P450 2C9 (CYP2C9) is one of the most abundant CYP enzymes in the human liver. CYP2C9 metabolizes more than 100 therapeutic drugs, including tolbutamide, glyburide, diclofenac, celecoxib, torasemide, phenytoin losartan, and S-warfarin). Some natural and herbal compounds are also metabolized by CYP2C9, probably leading to the formation of toxic metabolites. CYP2C9 also plays a role in the metabolism of several endogenous compounds such as steroids, melatonin, retinoids and arachidonic acid. Many CYP2C9 substrates are weak acids, but CYP2C9 also has the capacity to metabolise neutral, highly lipophilic compounds. A number of ligand-based and homology models of CYP2C9 have been reported and this has provided insights into the binding of ligands to the active site of CYP2C9. Data from the site-directed mutagenesis studies have revealed that a number of residues (e.g. Arg97, Phe110, Val113, Phe114, Arg144, Ser286, Asn289, Asp293 and Phe476) play an important role in ligand binding and determination of substrate specificity. The resolved crystal structures of CYP2C9 have confirmed the importance of these residues in substrate recognition and ligand orientation. CYP2C9 is activated by dapsone and its analogues and R-lansoprazole in a stereo-specific and substrate-dependent manner, probably through binding to the active site and inducing positive cooperativity. CYP2C9 is subject to induction by rifampin, phenobarbital, and dexamethasone, indicating the involvement of pregnane X receptor, constitutive androstane receptor and glucocorticoid receptor in the regulation of CYP2C9. A number of compounds have been found to inhibit CYP2C9 and this may provide an explanation for some clinically important drug interactions. Tienilic acid, suprofen and silybin are mechanism-based inhibitors of CYP2C9. Given the critical role of CYP2C9 in drug metabolism and the presence of polymorphisms, it is important to identify drug candidates as potential substrates, inducer or inhibitors of CYP2C9 in drug development and drug discovery scientists should develop drugs with minimal interactions with this enzyme. Further studies are warranted to explore the molecular determinants for ligand-CYP2C9 binding and the structure-activity relationships.

show abstract

Section: Drug-drug Interactions Owing To Induction Of Cyp2c9mentioning

confidence: 95%

Substrates, Inducers, Inhibitors and Structure-Activity Relationships of Human Cytochrome P450 2C9 and Implications in Drug Development

Zhou¹,

Zhou²,

Liu³

et al. 2009

CMC

149

View full text Add to dashboard Cite

show abstract

“…The most commonly prescribed inducers of drug metabolism are phenytoin, phenobarbital, and carba- mazepine. Ethanol, when used chronically, also induces drug metabolism [34]. The interaction between antipsychotic drugs and AEDs is complex.…”

Section: Drug Interactionsmentioning

confidence: 99%

Epilepsy in the elderly

Leppik

2001

Curr Neurol Neurosci Rep

View full text Add to dashboard Cite

The active prevalence rate of epilepsy among persons over 65 years of age is approximately 1.5%, about twice the rate in younger adults. Treatment of epilepsy in the elderly is complicated by alterations in drug metabolism, use of concomitant medications, and multiple medical problems. Drug interactions are a major issue, and a full knowledge of the isoenzyme profile and protein-binding characteristics of each drug (antiepileptic and other) must be known.

show abstract

“…The most commonly prescribed inducers of drug metabolism are phenytoin, phenobarbital, carbamazepine, and primidone. Ethanol, when used chronically, also induces drug metabolism [56].…”

Section: Drug Interactions With Non-aedsmentioning

confidence: 99%

Medical Management of Seizures in Cerebrovascular Disorders

Menon

Leppik

2015

Seizures in Cerebrovascular Disorders

View full text Add to dashboard Cite

Cerebrovascular disorders are one of the most common identifiable causes of epilepsy, especially in the elderly [1]. Seizures after a stroke can occur early, within 7-14 days [2-6], or late, after 14 days [7][8][9][10]. Early seizures do not necessarily progress to epilepsy, but may result in increased morbidity and mortality. Reports vary considerably regarding the incidence of single seizures and epilepsy after a stroke. In adults younger than 50 years of age, 12.7 % with ischemic strokes and 25.6 % with intracranial hemorrhage developed epilepsy. This study used the more recent definition of epilepsy, which is the occurrence of a single seizure associated with an enduring condition associated with epilepsy. Another large study reported the occurrence of seizures in 168 (8.9 %) of 1897 persons following an ischemic stroke and 28 (10.6 %) of 265 after a hemorrhagic stroke [4]. Most seizures occurred within 2 years of the stroke.A critical question addressing the issue of treatment is the occurrence of a second seizure after a single seizure. Unfortunately, this is a difficult question to answer from the literature. Many physicians initiate treatment with antiepileptic drugs (AEDs) following a single seizure because of the perception that there is a high risk of additional seizures in the context of stroke and seizure. Thus, reports of recurrent seizures are confounded with treatment, and it is difficult to establish the risk of epilepsy as defined by two or more unprovoked seizures. In one study by Arntz, 75 % of persons with an ischemic stroke and 80 % with a hemorrhagic stroke were

show abstract

Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics

Cited by 34 publications

References 1 publication

Substrates, Inducers, Inhibitors and Structure-Activity Relationships of Human Cytochrome P450 2C9 and Implications in Drug Development

Substrates, Inducers, Inhibitors and Structure-Activity Relationships of Human Cytochrome P450 2C9 and Implications in Drug Development

Epilepsy in the elderly

Medical Management of Seizures in Cerebrovascular Disorders

Contact Info

Product

Resources

About