Effects of age on meperidine disposition.

Elderly patients appear to be more sensitive to meperidine than younger ones; however, the contributions of altered dynamic and kinetic factors are not clear. Accordingly, seven healthy normal men aged 60 to 79 yr were simultaneously given 25 mg meperidine HCl intravenously and the same dose of deuterium-labeled drug either orally or intramuscularly (deltoid). Blood and urine samples collected over 24 hr were analyzed by gas chromatography-mass spectrometry and kinetic data were compared to those previously obtained in a young cohort. Systemic clearance (8.61 +/- 2.22 ml/min/kg), apparent oral clearance (17.5 +/- 5.5 ml/min/kg), terminal t1/2 (6.98 +/- 1.86 hr), and the blood/plasma concentration ratio (0.97 +/- 0.12) in the elderly did not differ from those in younger subjects. In the elderly, however, the initial (2.4 +/- 0.8 l/kg) and the steady-state (4.6 +/- 0.9 l/kg) volumes of distribution were 300% and 135% values in the young. No age differences were found in absorption profiles or bioavailability after oral (F = 0.49 +/- 0.08) or intramuscular (F = 0.94 +/- 0.04) dosing. It appears that age-related alterations in drug disposition per se do not account for changes in clinical efficacy of meperidine in the elderly.