Linked Life Data

8834414

Source:http://linkedlifedata.com/resource/pubmed/id/8834414

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1996-11-27
pubmed:abstractText
The single-dose (S-D) and steady-state (S-S) pharmacokinetics of nefazodone (NEF) and two of its pharmacologically active metabolites, hydroxynefazodone (HO-NEF) and m-chlorophenylpiperazine (mCPP), in healthy elderly (> 65 years) men and women (N = 12 each) were compared with those in healthy younger (18-40 years) men and women (N = 12 each). All subjects were classified as extensive metabolizers of dextromethorphan (cytochrome P4502D6). Subjects were administered a 300-mg dose of nefazodone hydrochloride for the evaluation of S-D pharmacokinetics. For the evaluation of S-S pharmacokinetics, 300-mg doses of NEF were administered twice daily (every 12 hours) for 8 days (single morning dose on day 8). Serial blood samples were collected after the single dose and the morning dose on day 8 of the twice-daily administration; a blood sample for trough level was collected from each subject just before the morning dose on days 2 to 8 of the twice-daily dosing to assess the attainment of steady state. Plasma samples were assayed for NEF, HO-NEF, and mCPP by a specific, validated high-performance liquid chromatography assay. After a single dose of NEF, the mean peak concentrations in plasma and the area under the curves (AUC) for NEF and HO-NEF were about twofold higher in elderly versus young subjects, but mean AUCs for mCPP were similar. Levels in plasma for NEF, HO-NEF, and mCPP reached steady state by day 3 of multiple dosing. At steady state, exposure to NEF and HO-NEF, based on AUC(TAU) values, was quite variable among age/gender groups but on the average was about 50% higher in elderly women compared with the other three groups of subjects; the exposure to mCPP at steady state was similar in elderly and young subjects. Because all subjects were extensive metabolizers, the effect of gender or age on the pharmacokinetics of NEF and its metabolites in poor metabolizers is not known. There were no serious or unexpected adverse experiences observed in this study. Assuming that similar systemic exposure to NEF and its active metabolites will result in similar therapeutic effects in young and elderly individuals, the difference in systematic exposure to NEF and HO-NEF in elderly subjects suggests that NEF treatment should be initiated at half the usual dose with titration upward and that the usual precautions exercised in treating elderly patients should be used.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0271-0749
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
19-25
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
A study of the effect of age and gender on the pharmacokinetics of nefazodone after single and multiple doses.
pubmed:affiliation
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey, USA.
pubmed:publicationType
Journal Article, Clinical Trial, Comparative Study