RT Journal Article
SR Electronic
T1 Alprazolam in Young and Elderly Men: Sensitivity and Tolerance to Psychomotor, Sedative and Memory Effects
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1317
OP 1329
VO 281
IS 3
A1 Richard J. Bertz
A1 Patricia D. Kroboth
A1 Frank J. Kroboth
A1 Ian J. Reynolds
A1 Firoozeh Salek
A1 C. Eugene Wright
A1 Randall B. Smith
YR 1997
UL http://jpet.aspetjournals.org/content/281/3/1317.abstract
AB This study was designed to determine whether age influences sensitivity to alprazolam and/or rate of acute tolerance development to the effects of alprazolam. Three treatments were each separated by 4 weeks. Twenty-five young (ages 22- 35) and 13 elderly (ages 65–75) men received 2 mg of alprazolam/2 min i.v. Blood samples were obtained over 48 hr, and sedative, psychomotor and memory effects were assessed serially for 12 hr. Clearance was lower (P = .05) and eliminationt [1/2] was longer (P = .005) in the elderly, but area under the concentration curve to 12 hr and maximum concentration did not differ by age group. Maximum impairment was greater in the elderly for all assessments. Mean EC50values differed between the elderly (25.3 and 25.0 ng/ml) and the young (39.8 and 36.5 ng/ml) on card sorting and digit symbol substitution, respectively (P < .001). Bolus treatment data were used to individualize doses for the crossover of placebo and alprazolam; infusions were designed to maintain a plateau alprazolam concentration between 1 and 9 hr. Alprazolam concentrations through 12 hr did not differ between the young and elderly. Mediant [1/2] for offset of effect for digit symbol substitution was 2.8 hr in the young and 4.9 hr in the elderly (P = .05). Therefore, aging decreases alprazolam clearance and increases sensitivity to effects of alprazolam through a mechanism other than pharmacokinetics; aging also decreases the rate of offset of effect of alprazolam. In addition, the data provide insight into the intensity of initial effect as a determinant of rate of tolerance development. The American Society for Pharmacology and Experimental Therapeutics