Reproducibility of antipyrine half-lives in elderly subjects

Vesell, Elliot S.; Deangelo, Theresa M; Katz, Ira R.

doi:10.1038/clpt.1993.126

Cited by 10 publications

(4 citation statements)

References 4 publications

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“…O'Malley et al (1971) were the ®rst to report that antipyrine metabolism is impaired in elderly subjects, describing signi®cant increases of mean antipyrine halflife in a group of 18 geriatric patients. This observation has been subsequently con®rmed by others who have found longer elimination half-lives in the elderly (Swift et al 1978;Vesell et al 1993), and who reported a reduction with age in both antipyrine clearance and volume of distribution (Bach et al 1981;Sotaniemi et al 1997). 25.0 (0.6) 23.2 (0.6)* O 2max (ml/min/kg) 28.2 (0.6) 29.0 (0.8) RI 9.1 (0.5) 6.8 (0.7)* * Signi®cantly dierent from preexercise value; P < 0.05 Previous studies by our group have con®rmed that aging is accompanied by a decline in the clearance of antipyrine and a signi®cant increase in antipyrine half-life both in men and women (Jorquera et al 1995;.…”

Section: Discussionmentioning

confidence: 68%

Physical exercise and improvement of liver oxidative metabolism in the elderly

et al. 2000

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Drug metabolizing capacity is generally reduced in the elderly, and physical exercise has been reported to increase drug oxidative metabolism. The purpose of this investigation was to study the effects of engagement in a program of regular physical exercise on the clearance and metabolite excretion of antipyrine, a marker of oxidative metabolism, in elderly subjects. The saliva clearance of antipyrine and the production clearances of antipyrine metabolites were studied in 37 elderly women (mean age 66 years). Subjects attended 60-min sessions three times a week for 12 weeks. Each session consisted of both aerobic (training of cardiorespiratory capacity) and nonaerobic (training of muscular strength/endurance and flexibility/coordination) exercises performed at 50-75% of maximum oxygen uptake. Antipyrine was administered orally and pharmacokinetic parameters were obtained from saliva and urine samples. After 3 months of participation in the exercise program, salivary antipyrine clearance was significantly increased by 17% mean (SEM) 0.42 (0.02) vs 0.36 (0.02) ml/min/kg; P < 0.05) and the half-life of antipyrine was significantly reduced by 18% (17.9 (1.1) vs 22.3 (1.3) h; P < 0.05). No significant change with exercise was observed in the renal clearance of antipyrine or in the norantipyrine formation clearance, but significant increases were found for hydroxymethylantipyrine [42 (5) vs 32 (4) microl/kg/min; P < 0.05; +31%] and 4-hydroxyantipyrine [243 (18) vs 194 (17) microl/kg/min; P < 0.05; +25%] formation clearances. These findings indicate that regular exercise leads to increased disposition of antipyrine in the elderly and that the main metabolic pathways of the compound are changed differentially.

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Section: Discussionmentioning

confidence: 68%

Physical exercise and improvement of liver oxidative metabolism in the elderly

et al. 2000

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“…It turned out that Elliot Vesell in several of his important studies of human drug metabolism in twins and unrelated individuals had measured pharmacokinetic data following repeated drug administration; he used repeat studies to establish consistently of response as a means to validate twin investigations Page 1968a-c, 1969;Penno et al, 1981;Vesell and Penno 1983;Vesell et al, 1993]. He found it easier to control consistency and safety of single doses to twin subjects than repeat administrations to unrelated subjects.…”

Section: Twin Studies and The Proposed Repeat Testmentioning

confidence: 99%

Repeat Administration of Drugs as a Means to Assess the Genetic Component in Pharmacological Variability

Kalow

Endrényi

Tang³

1999

Pharmacology

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“…In particular, antipyrine decay from plasma has been traditionally used as a sensitive tool to estimate the effect of genetic factors [26,27], disease states [28][29][30], dietary habits [31,32], drugs, and a variety of host factors [31,33] on the oxidative ability of the liver. Three major metabolic pathways account for most of antipyrine elimination and each of these biotransformation reactions may be mediated through a different cytochrome P450 subfamily [24,34]. Thus, the complexity of antipyrine disposition, with the involvement of multiple enzymatic systems, clearly distinguishes antipyrine from other model drugs such as debrisoquin and mephenytoin, the metabolism of which is thought to reflect predominantly the activity of CYP2D6 and CYP2C19 respectively [35].…”

Section: Discussionmentioning

confidence: 99%

Antipyrine disposition in obesity: evidence for negligible effect of obesity on hepatic oxidative metabolism

Caraco

Zylber‐Katz

et al. 1995

Eur J Clin Pharmacol

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Following an overnight fast and 2 days of abstention from caffeine, a single 1.0-g oral dose of antipyrine was administered to 20 obese but otherwise healthy subjects (group A) and 11 healthy volunteers (group B). Weight, Body Mass Index (BMI) and % of Ideal Body Weight (IBW) were significantly greater in the obese than in the lean group. (Mean 110.4 vs 62.7 kg; 38.5 vs 22.3 kg.m-2 and 181 vs 106% respectively). In a subgroup of 6 obese subjects (group C) antipyrine was given again 11.3 months later after a 29.8 kg mean weight loss. Antipyrine apparent volume of distribution (V) and elimination half-life (t1/2) were significantly greater in the obese than in the lean group (V 49.9 vs 34.3 l respectively; t1/2 15.5 vs 12.0 h respectively), but its clearance rate (CL0) values were similar. V corrected for total body weight was significantly reduced in group A than in group B (0.45 vs 0.55 l.kg-1 respectively). Stratified comparison of antipyrine pharmacokinetics between obese and lean subjects according to age, gender and smoking habits did not alter the overall results. In group C, weight reduction was associated with a significant decrease in antipyrine V (from 51.8 to 47.5 l) and t1/2 (from 15.1 to 12.7 h), and a non-significant increase in antipyrine CL0. We conclude that in severely obese subjects, antipyrine total V is mildly increased but V corrected for total body weight is significantly decreased. In addition, obesity is associated with a slight prolongation of antipyrine t1/2 whereas its CL0 is unaltered. These findings may indicate that obesity, even in its extreme form, has a negligible effect on the oxidative metabolic capacity of the liver.

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Reproducibility of antipyrine half-lives in elderly subjects

Cited by 10 publications

References 4 publications

Physical exercise and improvement of liver oxidative metabolism in the elderly

Physical exercise and improvement of liver oxidative metabolism in the elderly

Repeat Administration of Drugs as a Means to Assess the Genetic Component in Pharmacological Variability

Antipyrine disposition in obesity: evidence for negligible effect of obesity on hepatic oxidative metabolism

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