RT Journal Article
SR Electronic
T1 Imipramine and desipramine disposition in the elderly.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 183
OP 188
VO 232
IS 1
A1 Abernethy, D R
A1 Greenblatt, D J
A1 Shader, R I
YR 1985
UL http://jpet.aspetjournals.org/content/232/1/183.abstract
AB Forty-six healthy male and female volunteers aged 21 to 88 received single 12.5-mg i.v. doses of imipramine, and 35 of these people received single 50-mg p.o. imipramine doses on a different occasion. Thirty-five similar volunteers received single 50-mg p.o. desipramine doses. Among these subjects 25 participated in studies of both imipramine and desipramine. Kinetic variables for the respective drugs were determined from multiple plasma drug concentrations from samples obtained during 96 hr after the dosage. Imipramine half-life was markedly prolonged in elderly vs. young males (28.6 vs. 16.5 hr; P less than .001) and females (30.2 vs. 17.8 hr; P less than .01) due to decreased clearance (males: 567 vs. 945 ml/min, P less than .01; females: 599 vs. 975 ml/min, P less than .005) with no change in volume of distribution. After p.o. imipramine doses time to peak imipramine concentration was shorter in elderly females (2.1 vs. 4.8 hr; P less than .005) but no different in males. Peak concentration achieved was greater in the elderly of both sexes (males: 40.2 vs. 19.5 ng/ml, P less than .005; females: 44.7 vs. 10.4 ng/ml, P less than .01). Comparison of p.o. and i.v. imipramine doses indicated no difference in absolute bioavailability between the elderly and young of either sex. In contrast, after p.o. desipramine more limited age-related changes were noted. Desipramine half-life was slightly prolonged in elderly males (30.8 vs. 21.2 hr; P less than .05) apparently related to a nonsignificant decrease in p.o. clearance.(ABSTRACT TRUNCATED AT 250 WORDS)