Pharmacologic Aspects of Aging: A Survey of the Effect of Increasing Age on Drug Activity in Adults

Bender, A. Douglas

doi:10.1111/j.1532-5415.1964.tb00344.x

Cited by 64 publications

(22 citation statements)

References 78 publications

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“…These results may be related to the decreased ratio of liver weight to body weight and probably a possible decrease in the rate of hepa tic blood flow in the old mice (14)(15)(16). On the other hand, there was no marked age difference in the toxicity of strychnine.…”

Section: Discussionmentioning

confidence: 99%

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Studies on Age Difference in Mice for the Activity of Drug-Metabolizing Enzymes of Liver Microsomes

Kato

Takanaka

Onoda

1970

Japanese Journal of Pharmacology

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In previous papers, we reported that the activity of drug-metabolizing enzymes was higher in young female rats than in old female rats and that the duration of hexo barbital anesthesia was shorter in the young females than in the old females (1-3). More over, it was observed that the induction of microsomal drug-metabolizing enzymes by phenobarbital was more effective in young rats than in old rats (4,5).In the present communication, we wish to report the evidence that, in contrast to the results obtained with rats, clear age difference was not observed in the activity of drug-metabolizing enzymes in mice and there was no clear age difference in the induc tion of drug-metabolizing enzymes by phenobarbital. MATERIALS AND METHODSMale mice of ICR strain were used, unless otherwise specified. Phenobarbital (80 mg/kg) was given intraperitoneally 48 and 24 hours before sacrifice. Pooled liver from 3 mice was used for the preparation of each homogenate. Preparation of post mitochondrial and microsomal fractions was carried out as described in a previous paper (6). The activity of drug-metabolizing enzymes of liver microsomes was assayed as described in the previous paper (6). The hydroxylation of hexobarbital was determined by measuring the disappearance of the substrate according to the method of Cooper and Brodie (7). The N-demethylation of aminopyrine was determined by the forma tion of 4-aminoantipyrine (La Du et al.) (8). The hydroxylation of aniline was deter mined by the formation of p-aminophenol according to the method described by Kato and Gillette (9). The nitroreduction of p-nitrobenzoic acid was determined by measur ing the p-aminobenzoic acid formed according to the method of Fouts and Brodie (10). NADPH-cytochrome c reductase was determined according to the method of Williams and Kamin (11). NADPH-neotetrazolium reductase was assayed as described in the previous paper (2). The contents of microsomal protein and cytochrome P-450 were determined by the method of Lowry et al. (12) and Omura and Sato (13), respective ly. The duration of hexobarbital anesthesia and zoxazolamine paralysis was determined by the loss of the righting reflex. Strychnine toxicity was evaluated by the convulsion rate and mortality.

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Section: Discussionmentioning

confidence: 99%

“…There are some papers which demonstrate the differences of the drug effect and toxicity in aged subject from these in young one in animal experiments and in clinics (1,3,(14)(15)(16).…”

Section: Discussionmentioning

confidence: 99%

Studies on Age Difference in Mice for the Activity of Drug-Metabolizing Enzymes of Liver Microsomes

Kato

Takanaka

Onoda

1970

Japanese Journal of Pharmacology

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“…In general terms a lipophilic drug will distribute widely across membranes and will accumulate particularly in adipose tissue. Since the ratio of adipose to lean tissue increases with age (Bender, 1964) it would not be unexpected to find lipophilic drugs demonstrating a greater VdSS in the elderly. Prazosin has, in fact, only modest lipophilic properties (Taylor et al, 1977) and its 40% greater Vdss in the elderly is presumably a reflection of this fact when viewed against the 200-300% changes seen with the far more lipophilic drug diazepam.…”

Section: Discussionmentioning

confidence: 99%

Prazosin disposition in young and elderly subjects.

Rubin¹,

Scott²,

Reid³

1981

Brit J Clinical Pharma

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1 The disposition of prazosin following oral and intravenous administration has been studied in seven young and seven elderly men, all of whom were in good health and living independently in the community. 2 The elimination half-life (min) of prazosin was 123 + 19.4 (s.d.) in the young and 194 + 36 in the elderly (P < 0.01). 3 Clearance (ml min-m kg-') was 3.94 + 0.73 in the young and 3.53 + 1 in the elderly (P > 0.1). Volume of distribution at steady state (1 kg-') was 0.63 + 0.14 in the young and 0.89 + 0.26 in the elderly (P < 0.05). 4 The absolute bioavailability of orally administered prazosin was 0.68 -+ 0.17 in the young and 0.48 + 0.16 in the elderly (P < 0.05). 5 The significant increase in prazosin half-life in the elderly results from an increased volume of distribution, not from decreased clearance. 6 Gastrointestinal absorption of prazosin decreases in old age.

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“…1). Information on age-induced changes in drug disposition and elimination in man is limited, despite the observations that elderly patients often exhibit an apparent sensi- tivity to various therapeutic agents (31,32). Modest increases in the plasma half-life of antipyrine (33), phenylbutazone (33), and aminopyrine (34) in older individuals have been reported previously.…”

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confidence: 99%

The effects of age and liver disease on the disposition and elimination of diazepam in adult man.

Klotz¹,

Avant²,

Hoyumpa³

et al. 1975

J. Clin. Invest.

646

104

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Pharmacologic Aspects of Aging: A Survey of the Effect of Increasing Age on Drug Activity in Adults

Cited by 64 publications

References 78 publications

Studies on Age Difference in Mice for the Activity of Drug-Metabolizing Enzymes of Liver Microsomes

Studies on Age Difference in Mice for the Activity of Drug-Metabolizing Enzymes of Liver Microsomes

Prazosin disposition in young and elderly subjects.

The effects of age and liver disease on the disposition and elimination of diazepam in adult man.

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