caa a22 4500 465739210 CHVBK 20180323111803.0 cr unu---uuuuu 170327e19900401xx s 000 0 eng 10.1007/BF02243999 doi (NATIONALLICENCE)springer-10.1007/BF02243999 Alprazolam in the elderly: pharmacokinetics and pharmacodynamics during multiple dosing [Elektronische Daten] [Patricia Kroboth, James McAuley, Randall Smith] Previous studies have suggested that elderly men eliminate alprazolam more slowly than young adults. This study in the elderly was designed to determine whether a change in pharmacokinetics influences the response to alprazolam during multiple dose regimens. In addition, the study was designed to determine alprazolam pharmacokinetics and the degree to which its hydroxymetabolites accumulate, the degree of psychomotor impairment, and whether tolerance to impairment and sedation develops during three different multiple dose regimens. Twenty-six subjects completed this study. The subjects were randomized into one of three treatment groups: 0.25 mg q8h, 0.5 mg q8h, and 2 mg q12h. Subjects remained in the clinic for 8 days (day — 2-day 5). Day 0 was used as a drug free testing day to establish baseline scores for sedation, digit symbol substitution (DSS), card sorting (CS) tasks, and two computer tests. Subjects received the drug according to schedule on days 1 through 4, with day 5 as the washout day. Blood samples were assayed for alprazolam, alpha-hydroxyalprazolam and 4-hydroxyalprazolam. Alpha-hydroxyalprazolam concentrations were below assay detection limits in all subjects in the 0.25 and 0.5 mg q8h groups and ≤2.6 ng/ml in the 2 mg q12h group. When detectable, 4-hydroxyalprazolam concentrations were <10% of the corresponding alprazolam concentration. Mean alprazolam oral clearance values in the three treatment groups ranged between 0.54 and 0.62 ml/min/kg and half-lives were in excess of 21 h. Degree of sedation and impairment was dose related. Sedation and impairment was not higher on day 4 despite concentrations 2-3 times as great as on day 1, indicating development of tolerance. Subjects were not, however, back to baseline level of performance on day 4. Springer-Verlag, 1990 Alprazolam nationallicence Elderly nationallicence Geriatrics nationallicence Pharmacokinetics nationallicence Pharmacodynamics nationallicence Kroboth Patricia Department of Pharmacy Practice and Center for Pharmacodynamic Research, University of Pittsburgh, 15261, Pittsburgh, PA, USA aut McAuley James Department of Pharmacy Practice and Center for Pharmacodynamic Research, University of Pittsburgh, 15261, Pittsburgh, PA, USA aut Smith Randall Clinical Pharmacokinetics Research Unit, The Upjohn Company, 49001, Kalamazoo, MI, USA aut Psychopharmacology Springer-Verlag 100/4(1990-04-01), 477-484 0033-3158 100:4<477 1990 100 213 https://doi.org/10.1007/BF02243999 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF02243999 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Kroboth Patricia Department of Pharmacy Practice and Center for Pharmacodynamic Research, University of Pittsburgh, 15261, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- McAuley James Department of Pharmacy Practice and Center for Pharmacodynamic Research, University of Pittsburgh, 15261, Pittsburgh, PA, USA aut NATIONALLICENCE 700 1- Smith Randall Clinical Pharmacokinetics Research Unit, The Upjohn Company, 49001, Kalamazoo, MI, USA aut NATIONALLICENCE 773 0- Psychopharmacology Springer-Verlag 100/4(1990-04-01), 477-484 0033-3158 100:4<477 1990 100 213 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer