Linked Life Data

12021622

Source:http://linkedlifedata.com/resource/pubmed/id/12021622

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-5-21
pubmed:abstractText
The authors assessed the effect of concomitant antiepileptic therapy on steady-state plasma concentrations of the new antiepileptic drug (AED) topiramate and the potential relation between topiramate plasma levels and side effects in a cohort of 116 patients with epilepsy. On the basis of concomitant AEDs, patients were divided into two subgroups, otherwise comparable for age and weight-adjusted daily dose of topiramate. Group A (n = 73) received topiramate plus AED inducers of cytochrome P450 (CYP) metabolism, such as carbamazepine, phenobarbital, and phenytoin. Group B (n = 43) received topiramate plus AEDs without inducing properties of CYP metabolism (namely valproic acid and lamotrigine). Weight-normalized topiramate clearance values, calculated as dosing rate/steady-state plasma drug concentration, were about 1.5-fold in patients receiving AED inducers compared with patients receiving AED noninducers. Topiramate plasma concentrations were linearly related to daily drug doses, regardless of concomitant AED therapy, over a dose range from 25 to 800 mg/d, although, at a given daily dose, a large interpatient variability was observed in matched plasma drug concentrations within each group of patients. Thirty-nine patients (34%) reported side effects associated with topiramate, mostly central nervous system effects. No consistent relation was observed between topiramate plasma concentrations and adverse effects, either in the cohort of patients as a whole or within each subgroup. From a clinical point of view, patients receiving concurrent treatment with enzyme-inducing AEDs can show twofold lower topiramate plasma concentrations compared with patients receiving valproic acid or lamotrigine, and appropriate topiramate dosage adjustments may be required when concomitant AED inducers are either added or withdrawn. Due to the observed variability in topiramate metabolic variables and the complex spectrum of possible pharmacokinetic and pharmacodynamic interactions with the most commonly coprescribed AEDs, monitoring of plasma topiramate concentrations may help the physician in the pharmacokinetic optimization of the drug dosage schedule in individual patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0163-4356
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
332-7
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed-meshheading:12021622-Adult, pubmed-meshheading:12021622-Anticonvulsants, pubmed-meshheading:12021622-Carbamazepine, pubmed-meshheading:12021622-Child, pubmed-meshheading:12021622-Child, Preschool, pubmed-meshheading:12021622-Dose-Response Relationship, Drug, pubmed-meshheading:12021622-Drug Administration Schedule, pubmed-meshheading:12021622-Drug Interactions, pubmed-meshheading:12021622-Drug Monitoring, pubmed-meshheading:12021622-Drug Therapy, Combination, pubmed-meshheading:12021622-Epilepsy, pubmed-meshheading:12021622-Female, pubmed-meshheading:12021622-Fructose, pubmed-meshheading:12021622-Humans, pubmed-meshheading:12021622-Male, pubmed-meshheading:12021622-Phenobarbital, pubmed-meshheading:12021622-Phenytoin, pubmed-meshheading:12021622-Prospective Studies, pubmed-meshheading:12021622-Triazines, pubmed-meshheading:12021622-Valproic Acid
pubmed:year
2002
pubmed:articleTitle
Topiramate therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs.
pubmed:affiliation
Laboratory of Clinical Neuropharmacology, Department of Neurological Sciences, University of Bologna, Via Foscolo 7, 40123 Bologna, Italy. contin@neuro.unibo.it
pubmed:publicationType
Journal Article, Clinical Trial, Controlled Clinical Trial