The influence of age and smoking on the elimination of disopyramide.

Bonde, Jan; Pedersen, L. E.; Bødtker, Søren; Angelo, H. All; Tl, Svendsen; Jp, Kampmann

doi:10.1111/j.1365-2125.1985.tb05096.x

Cited by 30 publications

(6 citation statements)

References 24 publications

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“…Bredesen and Kierulf (1984) could not detect a correlation between the binding of disopyramide or its major metabolite (mono-N-dealkyldisopyrarnide) and age in 60 patients (l6 to 89 years) with unspecified disease states. Bonde et al (1985) reported the same percentage free (30%) for disopyramide in healthy young volunteers and elderly patients. Holt et al (1983), however, reported a higher percentage bound in geriatric patients (76.2% bound) than in healthy adults (65.7%).…”

Section: Disopyramidementioning

confidence: 50%

Plasma Protein Binding of Drugs in the Elderly

Wallace

Verbeeck

1987

Clinical Pharmacokinetics

120

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Binding to plasma proteins can affect the pharmacokinetics and pharmacodynamics of drugs. Age is one of many factors which can affect plasma protein binding of drugs. Unfortunately, very few generalities can be drawn from the studies of the effect of age on protein binding. Whether age has an effect on protein binding is dependent not only on the drug, but also on the manner in which the study is conducted. Several studies involve patients with various disease states making assessment of the effect of age alone on protein binding difficult. Results of different studies on the same drug do not always agree--in one case finding no change in protein binding with age and in another, a significant increase or decrease in protein binding. Most drugs which exhibit increased binding (decreased free fraction) in elderly subjects are basic and tend to have a greater affinity for alpha 1-acid glycoprotein than for albumin. The list of drugs exhibiting decreased binding (increased free fraction) in the elderly is longer and includes both acidic and basic drugs. The impact of changes in protein binding with age is dependent on the magnitude of the change, on the pharmacokinetic characteristics of the drug and on its therapeutic index. Some changes, although statistically significant, are not likely to be of importance clinically. From the studies reviewed, the free fraction is changed by greater than 50% in the elderly for only a few drugs, e.g. acetazolamide, diflunisal, etomidate, naproxen, salicylate, valproate and zimeldine.

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Section: Disopyramidementioning

confidence: 50%

Plasma Protein Binding of Drugs in the Elderly

Wallace

Verbeeck

1987

Clinical Pharmacokinetics

120

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“…This type of an exaggerated response in old animals was cited by Adelman (1975); however, he did not specifically discuss it. Although the effect of enzyme inducers on drug metabolism in elderly humans is controversial in the literature (Kitani, 1988), a greater enzyme induction in old than in young humans has been reported (Bonde et al 1985). It is questionable whether this type of response can be classified as one type of disrupted enzyme regulation in old age.…”

Section: What Really Declines With Age?mentioning

confidence: 99%

What really declines with age?

Kitani¹

2007

AGE

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In order to understand the basic mechanisms underlying the organismic aging process, considerable efforts have been devoted in the last half-century to biochemical (enzyme activity) alterations in specific tissues and organs of various organisms associated with aging. When a decline in enzyme activities with age has been found in a study, especially for key enzymes such as antioxidant enzymes, the results have often been interpreted as a cause for the aging of the entire body. Retrospectively, however, these changes turned out to be so variabledepending on species, strains and sexes of animalsthat the interpretation of these results in general terms of aging became invalid. Further, unlike the prediction for the whole human body, many enzyme activities in a vital organ, such as the liver, remained unchanged, as long as the old subjects remained healthy. However, enzyme activities in old animals and humans are often more susceptible to morbidities and frailties, which themselves are often accompanied by infections and malnutrition. Despite the rather stable enzyme functions in the liver with age, a distinct and progressive decline in the lateral diffusion coefficient of proteins of hepatocyte plasma membranes has been demonstrated by fluorescence recovery after photobleaching (FRAP), which was implicated as the cause for the decline of hepatocyte functions such as ouabain (and taurocholate) hepatic uptake and their eventual biliary excretion. Since a similar decline in protein diffusion coefficients was observed in brain and muscle cells, it is likely that these changes are occurring in common with many cell types of the body, thus causing a delay in transmembrane transport of endogenous and exogenous substances whose transports are mediated by membrane proteins. In attempts to prolong the life spans of animals other than by calorie restriction, but instead using deprenyl or tetrahydrocurcumin, works by the author and coworkers are introduced and discussed. Despite limited success along these lines thus far, further attempts are encouraged, primarily to understand the mechanisms underlying organismic aging processes and to find a practical way to prolong the health span of the elderly.

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“…1988Cusack et al 1980;Vestal el al. 1987) and disopyramide (Bonde et al 1985) suggest that the induction effect of cigarette smoking remains in old age. The magnitude of Ihis induction effect is significant; the difference in clearance between elderl y smokers and nonsmokers was about 30% for disopyramide (Bonde et al 1985), and up to 77% in the case of theophylline (Crowley ct al.…”

Section: Tobacco Smoking and Drug Metabolismmentioning

confidence: 99%

Hepatic Drug Metabolism and Aging

Durnas

Loi

Cusack

1990

Clinical Pharmacokinetics

175

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Although there is considerable variation in the effect of age on drug biotransformation, the metabolism of many drugs is impaired in the elderly. Age-related physiological changes, such as a reduction in liver mass, hepatic metabolising enzyme activity, liver blood flow and alterations in plasma drug binding may account for the decreased elimination of some metabolised drugs in the elderly. It is difficult, however, to separate an effect of aging from a background of marked variation in the rate of metabolism due to factors such as individual metabolic phenotype, environmental influences, concomitant disease states and drug intake. The prevailing data suggest that initial doses of metabolised drugs should be reduced in older patients and then modified according to the clinical response. In most studies the elderly appear as responsive as young individuals to the effects of compounds which induce or inhibit the activity of cytochrome P450 isozymes. Concurrent use of other agents, which induce or inhibit drug metabolism, mandates dose adjustment as in younger patients. Many questions remain unanswered. For instance, limitations of in vitro studies prevent any firm conclusion about changes in hepatic drug metabolising enzyme activity in the elderly. With aging, some pathways of drug metabolism may be selectively affected, but this has not been adequately scrutinised. The possibility that metabolism of stereoisomers may be altered in the elderly has not been adequately tested. The effect of aging on the distribution of polymorphic drug metabolism phenotypes is still not established, despite potential implications for disease susceptibility and survival advantage.

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The influence of age and smoking on the elimination of disopyramide.

Cited by 30 publications

References 24 publications

Plasma Protein Binding of Drugs in the Elderly

Plasma Protein Binding of Drugs in the Elderly

What really declines with age?

Hepatic Drug Metabolism and Aging

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