Linked Life Data

10770460

Source:http://linkedlifedata.com/resource/pubmed/id/10770460

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-6-28
pubmed:abstractText
In an open clinical trial, serum concentrations of haloperidol pyridinium (C(HP+)) and reduced haloperidol pyridinium (C(RHP+)), as well as haloperidol (CH) and reduced haloperidol (C(RH)), were measured in 57 schizophrenic and schizoaffective inpatients during 6 weeks of short-term treatment. Psychopathology was monitored with the Brief Psychiatric Rating Scale (BPRS), and extrapyramidal adverse effects were assessed with the Extrapyramidal Symptom Rating Scale (EPS). Significantly linear relationships were found between haloperidol dose (D) and pyridinium metabolite serum concentrations, as well as between C(H) and the pyridinium metabolite serum concentrations. C(HP+) (range, 0.2-4.9 ng/mL) and C(RHP+) (range, 0.03-6.23 ng/mL) were low compared with C(H) and C(RH), being as mean values approximately 7% and 14% of C(H) and C(RH), respectively. Additionally, the values of C(RHP+) and the slope of the correlation of C(H) with the C(RHP+)/C(HP+) ratio were considerably lower than in a previous report of long-term treatment with haloperidol. This is explained by the shorter time of treatment of the present study. Carbamazepine comedication was found to not influence relative pyridinium metabolite serum concentrations C(HP+)/D and C(RHP+)/D. However, the aromatization ratios of haloperidol (C(HP+)/C(H)) and reduced haloperidol (C(RHP+)/C(RH)) were increased by concomitant carbamazepine. As the main result, no relationships between the pyridinium metabolite serum concentrations and clinical variables (BPRS change, EPS, dose of biperiden) were detected. For instance, the aromatization ratios C(HP+)/C(H) and C(RHP+)/C(RH) did not predict clinical improvement or extrapyramidal adverse effects. Therefore, no confirmation of the "pyridinium hypothesis," which suggests haloperidol pyridinium metabolites to be the origin of adverse effects and decreased therapeutic effect, can be derived from this study. However, the authors emphasize that pyridinium metabolites cannot be excluded as the origin of decreased therapeutic effect in long-term treatment and of adverse effects not investigated in the present study, such as tardive dyskinesia. Finally, it is concluded that the serum concentration of the parent drug remains the main variable of interest in the therapeutic drug monitoring of haloperidol during short-term treatment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0271-0749
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
210-9
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Disposition of haloperidol pyridinium and reduced haloperidol pyridinium in schizophrenic patients: no relationship with clinical variables during short-term treatment.
pubmed:affiliation
Institute of Clinical Pharmacology, University Hospital, Otto-von-Guericke University, Magdeburg, Germany. sven.ulrich@medizin.uni-magdeburg.de
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, Non-U.S. Gov't