Linked Life Data

14659489

Source:http://linkedlifedata.com/resource/pubmed/id/14659489

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4-5
pubmed:dateCreated
2003-12-8
pubmed:abstractText
Clozapine is an effective atypical antipsychotic drug applied in the treatment of resistant schizophrenia. The drug is mainly metabolized by cytochrome P-450 (CYP) enzymes especially the isozyme CYP1A2. Remarkably, the effective dosage varies widely among patients, making it necessary to individualize drug therapy with clozapine. The explanation for dosage variation may be differences in drug metabolism, and more specifically of CYP1A2 activity. This study is aimed at determining to what extent variability in clozapine dose can be explained by pharmacokinetic (PK) factors and more specifically by CYP1A2 activity in effectively treated psychiatric patients. In 22 evaluable patients with a schizophrenic disorder chronically using clozapine, the CYP1A2 activity and the clozapine clearance were estimated. For calculation of the pharmacokinetic parameters of clozapine, population PK software based upon Bayesian analysis was used. Caffeine clearance was estimated with the paraxanthine/caffeine ratio and served as estimate of CYP1A2 activity.A significant linear relationship was found between the clozapine dose and clozapine clearance (R: 0.71; P<0.05), whereas no relationship was found between clozapine dosage and clozapine serum trough concentration. Moreover, individual caffeine and clozapine clearances were found to be significantly related (R: 0.62; P<0.05) as were clozapine dose per kg body weight and P/C mol ratio (R: 0.44; P<0.05). We conclude that CYP1A2 activity is an important determinant of the variability of effective clozapine doses in psychiatric patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0928-0987
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
451-7
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
CYP1A2 activity is an important determinant of clozapine dosage in schizophrenic patients.
pubmed:affiliation
Department of Clinical Pharmacy, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, NL 1105 AZ Amsterdam, The Netherlands.
pubmed:publicationType
Journal Article, Clinical Trial