Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1984-12-18
pubmed:abstractText
While naproxen pharmacokinetics appear to be altered in the presence of both diminished renal and hepatic function, the degree to which naproxen disposition might be influenced in the elderly by concurrent alteration in these functions is not obvious. Total plasma clearance/bioavailability (CL/F) of naproxen after a single 375 mg oral dose was found to be less in a group of 10 healthy men between 66 and 81 years of age than in 10 healthy men between 22 and 39 years (0.318 +/- 0.078, 0.416 +/- 0.061 l/h). At steady state (375 mg, 12 hourly), however, CL/F was statistically indistinguishable between the two groups. The fraction of naproxen unbound to plasma protein was doubled in elderly subjects, both at peak and trough drug concentrations. The lowered protein binding tended to obscure a 50% decrement in the intrinsic clearance of naproxen in the elderly as estimated by unbound clearance/bioavailability (213 +/- 64, 396 +/- 155 l/h). As a result, mean steady-state plasma concentrations of naproxen were indistinguishable between the elderly and young (64.2 +/- 8.5, 58.2 +/- 8.1 mg/l) but the elderly generated twice the mean steady-state unbound plasma drug concentration (0.157 +/- 0.039, 0.0859 +/- 0.0212 mg/l). Since it is the unbound drug concentration which appears in general to relate more closely to pharmacological and toxic effect, it may be advisable to reduce naproxen doses by half in the elderly, pending plasma drug concentration-response studies in this age group. If a similar perturbation with age occurs in benoxaprofen protein binding as was observed with naproxen, benoxaprofen intrinsic clearance in the elderly might be only one quarter of that in younger individuals; a factor which may contribute to the toxicity of this drug in the elderly.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-1096900, http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-1206477, http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-1244564, http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-359314, http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-4624708, http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-6122789, http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-6462187, http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-650423, http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-6663482, http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-6930483, http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-7075118, http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-7084284, http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-7094505, http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-710028, http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-7190433, http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-731416, http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-7380943, http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-7439246, http://linkedlifedata.com/resource/pubmed/commentcorrection/6487459-7452451
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0306-5251
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
207-14
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
1984
pubmed:articleTitle
Naproxen pharmacokinetics in the elderly.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.