Fifty-one healthy volunteers aged 22 to 84 years received single 0.8 to 1.4 g i.v. doses of antipyrine. Kinetic variables were determined from multiple plasma antipyrine concentrations measured during 24 hr after dosage. Body weight increased with age, but antipyrine volume of distribution (in liters per kilogram) declined with age in men (r = -0.69, P < .01) and in women (r = -0.73, P < .01), probably reflecting a decline in relative lean body mass. Antipyrine clearance declined significantly with age in men (r = -0.64, P < .01), but the age-related change in women was less striking (r = -0.41, P < .05). Subjects also received single doses of the oxidized benzodiazepines diazepam (DZ) (n = 26), desmethyldiazepam (DMDZ) formed from prazepam (n = 18) or clorazepate (n = 13) and desalkylflurazepam (DAFLZ) formed from flurazepam (n = 15) and of conjugated benzodiazepines lorazepam (LRZ) (n = 17), oxazepam (OXZ) (n = 25) and temazepam (TMZ) (n = 29). Antipyrine half-life was highly correlated (P < .01) with that of DZ (r = 0.73), DMDZ (r = 0.83) and DAFLZ (r = 0.82), but not with LRZ (r = 0.13), OXZ (r = -0.12) or TMZ (r = -0.21). Antipyrine clearance also was significantly correlated with clearance of DZ (r = 0.59), but not with LRZ (r = -0.32), OXZ (r = 0.10) or TMZ (r = -0.07). Among oxidized benzodiazepines, half-life (and clearance) were highly intercorrelated (e.g., half-life of DZ vs. DMDZ, r = 0.77; DZ vs. DAFLZ, r = 0.90; DAFLZ vs. DMDZ, r = 0.93), as was clearance of conjugated benzodiazepines (e.g., clearance of OXZ vs. LRZ, r = 0.60; OXZ vs. TMZ, r = 0.80; LRZ vs. TMZ, r = 0.85). Antipyrine predicts reasonably well the capacity of healthy individuals to biotransform benzodiazepines metabolized by oxidative pathways, but does not accurately predict the capacity of such persons to metabolize benzodiazepines that undergo metabolism primarily by glucuronide conjugation.
|Original language||English (US)|
|Number of pages||7|
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|State||Published - 1982|
ASJC Scopus subject areas
- Molecular Medicine