{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T06:12:47Z","timestamp":1790489567747,"version":"4.1.0"},"reference-count":61,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,8,27]],"date-time":"2020-08-27T00:00:00Z","timestamp":1598486400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Age\u2010related changes in disposition of diazepam and its principal active metabolite, desmethyldiazepam (DMDZ), during and after extended dosage with diazepam were studied in healthy volunteers. Eight elderly subjects (ages 61\u201078 years) and 7 young subjects (21\u201033 years) received 2.5 mg of diazepam twice daily for 15 days. Predose (trough) concentrations of diazepam and DMDZ were measured during the 15 days of dosing, and in the postdosage washout period. Kinetic properties were determined by nonlinear regression using a sequential drug\u2010to\u2010metabolite pharmacokinetic model. Steady\u2010state plasma concentrations of diazepam and DMDZ were 30% to 35% higher in elderly subjects compared to young volunteers, and steady\u2010state clearances correspondingly lower, though differences did not reach significance. Large and significant differences were found between young and elderly groups in mean half\u2010life of diazepam (31 vs 86 hours; <jats:italic>P<\/jats:italic> &lt; .005) and DMDZ (40 vs 80 hours; <jats:italic>P<\/jats:italic> &lt; .02). Half\u2010life values from the multiple\u2010dose study were closely correlated with values from previous single\u2010dose studies of diazepam (R<jats:sup>2<\/jats:sup> = 0.85) and DMDZ (R<jats:sup>2<\/jats:sup> = 0.94) in the same subjects. With extended dosing of diazepam in the elderly, slow accumulation and delayed washout of diazepam and DMDZ is probable. After discontinuation, withdrawal or rebound effects are reduced in likelihood, but delayed recovery from sedative effects is possible due to slow elimination of active compounds. Safe treatment of elderly patients with diazepam is supported by understanding of age\u2010related changes in pharmacologic and pharmacokinetic properties.<\/jats:p>","DOI":"10.1002\/jcph.1726","type":"journal-article","created":{"date-parts":[[2020,8,28]],"date-time":"2020-08-28T14:45:41Z","timestamp":1598625941000},"page":"193-203","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Slow Accumulation and Elimination of Diazepam and Its Active Metabolite With Extended Treatment in the Elderly"],"prefix":"10.1002","volume":"61","author":[{"given":"David J.","family":"Greenblatt","sequence":"first","affiliation":[{"name":"Programs in Pharmacology and Drug Development and in Pharmacology and Experimental Therapeutics Tufts University School of Medicine  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerold 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