Phenazone (antipyrine) metabolism and distribution in young and elderly adults

Abstract

S U M M A R Y 1. The plasma half-life and apparent volume of distribution of phenazone (antipyrine) was studied in twenty-six normal adults (20-40 years of age) and twenty-six geriatric patients. 2.A wide range of values for plasma half-life was recorded in both groups (young 7.7-19.9 h, elderly 9.5-30.1 h) but the mean plasma half-life for the geriatric group (16.8 h; s.e.m. = 5.9) was significantly longer (P<O.Ol) than the normal adult group (12.5 h; s.e.m. = 3.2).3. No difference in plasma half-life was noted between sexes in either the geriatric or control groups.4. Doubling the dose of phenazone from 10 to 20 mg/kg made no difference to the plasma half-life in a subgroup of the geriatric patients.5. The volume of distribution of phenazone, representing total body water, was 0.59-0.63 I/kg in all groups except the elderly females, in whom it was 0.48 I/kg. This latter group showed a correspondingly higher plasma concentration extrapolated to time zero. 6. The difference in plasma half-life phenazone between normal adult and elderly groups is statistically significant, but the wide range of values in each group makes the biological significance less clear. Alteration of drug distribution with resultant higher plasma or tissue concentrations may contribute to adverse drug effects, particularly in the elderly female.

The Rate of Acetaminophen Metabolism in the Elderly and the Young

“…The observation reported here is similar to that already reported by us (13) with antipyrine, a drug with a longer half‐life than acetaminophen, and metabolized by hydroxylation in the hepatic microsomal system. In that study we found a threefold range of drug half‐life in each age group, with considerable group overlap, but again with a significant difference in the group means (elderly 16.8 hours, young 12.5 hours, p < .01).…”

Clinical pharmacology and the elderly patient

“…Hurwitz 7 showed a significant correlation between increasing age and adverse drug reactions from a total of 1160. The incidence in those aged [60][61][62][63][64][65][66][67][68][69] was twice that observed in those aged 30-39. Patients aged [70][71][72][73][74][75][76][77][78][79] had four times the incidence of those aged [30][31][32][33][34][35][36][37][38][39] (Table 2). o In a similar study Klein et al s indicated that there was an increased incidence of adverse reactions with age and although no detailed statistical analysis was attempted the results suggest that the incidence of adverse reactions in those aged more than 60 years was about three times that in patients aged less than 60 years.…”

Pharmacokinetics of molsidomine and of its active metabolite, SIN‐1 (or linsidomine), in the elderly

“…On the other hand, in so far as molsidomine is extensively metabolized in liver (Dell et al, 1978; Singlas et Martre, 1983;Bergstrand et al, 1984), an hepatic metabolism reduction, observed too in elderly subjects with other drugs such as antipyrine (Liddell et al, 1975 ;Wood et a!, 1979 ;Vestal et al, 1975), diazepam (Macklon et al, 1980 ;Klotz et al, 1975;Ochs et al, 1981) chlordiazepoxide (Roberts et al, 1978;Shader et al, 1977) quinidine (Ochs et al, 1978;Drayer et al, 1980) propranolol (Castleden and George, 1979;Rigby et al, 1985), famotidine (Lin et al, 1988) may be proposed to explain the molsidomine pharmacokinetic modifications in the elderly. Consistent with this hypothesis are the findings that molsidomine AUC is more markedly increased (3.4-fold) in elderly versus young volunteers that SIN-1 AUC (1.6-fold) and that molsidomine pharmacokinetic parameters are profoundly altered in cirrhotic patients (Spreux-Varoquaux et al, 1990).…”