Imipramine and desipramine disposition in the elderly

Area of Science:

• Pharmacokinetics
• Geriatric Pharmacology
• Drug Metabolism

Background:

• Age significantly influences drug pharmacokinetics.
• Understanding age-related changes in imipramine and desipramine is crucial for safe and effective prescribing in older populations.

Purpose of the Study:

• To investigate the pharmacokinetic differences of imipramine and desipramine between young and elderly healthy volunteers.
• To assess the impact of aging on drug clearance, half-life, and bioavailability.

Main Methods:

• Healthy male and female volunteers (aged 21-88) received single intravenous (i.v.) and oral (p.o.) doses of imipramine and oral doses of desipramine.
• Plasma drug concentrations were measured over 96 hours post-dosage.
• Key pharmacokinetic variables including half-life, clearance, volume of distribution, and time to peak concentration were determined.

Main Results:

• Imipramine half-life was markedly prolonged in elderly versus young volunteers (males and females) due to decreased clearance, with no change in volume of distribution.
• Elderly females showed a shorter time to peak imipramine concentration and higher peak concentrations after oral dosing.
• Absolute bioavailability of imipramine was similar between age groups.
• Desipramine exhibited only slight age-related changes in half-life and clearance.

Conclusions:

• Aging significantly alters imipramine pharmacokinetics, primarily through reduced clearance, leading to prolonged half-life and higher peak concentrations.
• These findings suggest potential for increased imipramine exposure and risk of adverse effects in the elderly.
• Desipramine appears to have a more favorable pharmacokinetic profile with less pronounced age-related alterations.