The effect of age and sex on metabolism and urinary excretion of antipyrine.

BACKGROUND: Drug-metabolizing capacity is generally reduced in the elderly. The purpose of this investigation was to study antipyrine clearance and metabolite excretion in old subjects of both sexes. METHODS: Saliva clearance of antipyrine and the production clearances of antipyrine metabolites were studied in young and elderly volunteers of both sexes. Seventy-six elderly subjects (mean age 81 years) were compared with a group of 24 young subjects (mean age 29 years). RESULTS: After oral administration, salivary antipyrine clearance declined with age in both males and females, whether or not this variable was corrected for weight, and antipyrine half-life was significantly prolonged in elderly groups of either sex. The percentage urinary excretion of the antipyrine metabolites (hydroxymethylantipyrine, HMA; norantipyrine, NORA; and 4-hydroxyantipyrine, OHA) was reduced at 48 h in the elderly compared to young subjects by 23%, 31%, and 10%, respectively, in males, and by 41%, 41%, and 24%, respectively, in females. The formation clearance of HMA was reduced by 47% in males and by 52% in females. NORA clearance declined by 42 and 56%, respectively, in males and females. A decrease of 30% in males and 44% in females was observed in OHA clearance. CONCLUSIONS: The findings suggest that aging leads to altered disposition of antipyrine in both males and females and that the main metabolic pathways of the compound are not different in the elderly.

[The effect of changes in nutritional status induced by age on oxidative liver metabolism]. / Influencia de los cambios en el estado nutritivo inducidos por la edad sobre el metabolismo oxidativo hepático.

INTRODUCTION: The hepatic oxidative metabolism is essential for the biotransformation of a large number substances, among which are found many drugs which are commonly used in clinical practice. The nutritional status of individuals has been shown to be of influence on this function. Aging produces a deterioration of the hepatic oxidative metabolism, without the cause for this situation having been clarified. Also, aging modifies the body composition of the individuals. The objective of this study is to evaluate whether the modifications which arise in the nutritive status due to age, can alter the hepatic oxidative capacity. MATERIAL AND METHODS: 165 elderly people of both sexes were studied, with an average age of 82 years, and 24 young people, with an average age of 29 years. All participants were subjected to a clinical questionnaire, along with an evaluation of anthropometric, biochemical, and immunological nutritive parameters. The study of the oxidative metabolism was conducted by evaluating the kinetics of antipyrine. RESULTS: The elderly people showed a decrease in the antipyrine clearance rate (Ap Cl) (P < 0.001), and a lengthening of their life-span (P < 0.05) with respect to the younger people. There was a significant correlation in the elderly people, between the Ap Cl and age, weight, size, the distribution volume, and the muscular area of the arm. A multiple regression analysis showed a predictive value which was independent for age, the AST, the lymphocytes, and size. CONCLUSION: Elderly people have a marked depression of the hepatic oxidative metabolism. The factors which participate in their nutritional situation, are of influence on this function. It is necessary to keep all the above in mind when it comes to prescribing drugs which require this type of biotransformation, in order to avoid adverse effects or drug interactions.

Accuracy of the one-sample method for determination of antipyrine clearance in elderly subjects.

The purpose of this study was to evaluate the validity of the one-sample abbreviated method for determination of the pharmacokinetic parameters of antipyrine in the elderly. Antipyrine pharmacokinetics were studied in 15 elderly women (mean age 86 years). Antipyrine (1 g) was administered orally and pharmacokinetic parameters were determined by the one-sample (24 h) and multiple-sample (3, 6, 9, 12 and 24 h) methods. Mean antipyrine clearance for the one-sample study (19.72 +/- 1.51) was almost identical to that obtained with the multiple-sample approach (20.73 +/- 1.57), and the two methods were very well correlated (r = 0.989). Relative standard deviations between individual clearances values for multiple-sample vs. one-sample studies averaged 1.6%. Values of elimination half-life were likewise very similar for the abbreviated (17.41 +/- 1.21) and complete (17.99 +/- 1.09) methods, with a significant correlation (r = 0.857). Although values were underestimated by 10% in the one-sample approach, no difference in the volume of distribution with the multiple-sample study was observed. When the unbiased volume of distribution value was determined from the total elimination curve against time, the influence of biased volume of distribution resulted in a 5.1% deviation in antipyrine clearance in the one sample method. The findings indicate that antipyrine pharmacokinetic parameters can be estimated with reasonable precision and accuracy in the elderly using a simplified one-sample procedure.

Effects of aging on antipyrine clearance: predictive factors of metabolizing capacity.

The purpose of this study was to identify variables that can account for the decline of antipyrine clearance (CLAP) in elderly adults and that may help predict a reduction in metabolizing capacity. For comparison, ClAP was determined in 177 elderly (mean age 82 years) and 25 young (mean age 29 years) volunteers. Antipyrine (1 g) was administered orally and ClAP was determined by the one-sample saliva method. Mean ClAP was reduced by 38% and antipyrine half-life increased by 64% in old subjects. Multiple regression analysis of ClAP revealed an independent value for age, serum aspartate transaminase (AST), and height in the elderly. The independent variables collectively accounted for 27% of the variance explained. Age, high serum AST, use of diuretics, and no consumption of drugs known to stimulate oxidative metabolism were selected by multivariate analysis (logistic model) as independent predictors of a low metabolizing capacity. The findings indicate that factors other than age may contribute to impaired hepatic oxidative metabolism in the elderly.

Assessment of antipyrine kinetics from saliva or plasma: influence of age.

The purpose of this study was to investigate whether antipyrine estimation in saliva provides valid information on plasma antipyrine clearance (APCl) and can be useful as an index of changes in drug metabolism with age. Antipyrine kinetics was studied in 93 elderly (mean age 82 years) and 23 young (mean age 29 years) volunteers. Plasma antipyrine half-life (APt1/2) increased and plasma APCl declined with age. No significant difference between plasma- and saliva-derived parameters was found in either young or old subjects. However, the saliva/plasma ACCl ratio tended to increase with age. A highly significant correlation between saliva and plasma APCl or APt1/2 was found in young subjects. Values were less closely related in the elderly and the slope of the saliva/plasma APCl relationship was significantly different in both groups of subjects. Residual variance was higher in the regressions corresponding to the elderly. The findings in the study indicate that the relationship between saliva and plasma kinetics in young subjects becomes less reproducible with age.

Antipyrine clearance in surgical patients maintained on hypocaloric peripheral parenteral nutrition.

BACKGROUND: Antipyrine clearance (CLAP) constitutes a sensitive indicator of hepatic microsomal enzyme activity providing specific information on hepatic function. The purpose of this study was to evaluate the influence of hypocaloric peripheral parenteral nutrition on CLAP in patients receiving nutrition support after elective surgery. METHODS: CLAP was measured in 15 patients before elective gastrointestinal surgery and 6 days after the surgery. Antipyrine (1 g) was administered orally, and CLAP was determined by the one-sample method. Subjects received a postoperative 786 kcal/d regimen providing 66 g of amino acid per day and 133 g of glucose per day for 5 days. Nutritional status was evaluated by anthropometric parameters. A control group of 15 patients received no postoperative hypocaloric peripheral parenteral nutrition but received conventional fluid therapy. RESULTS: Mean CLAP was increased by 61% (0.66 +/- 0.06 mL/min.kg-1 body wt vs 0.41 +/- 0.05 mL/min.kg-1 body wt in the preoperative period; p < .001), and antipyrine half-life was reduced by 42% (10.9 +/- 1.0 hours vs 18.9 +/- 2.0 hours; p < .001) after 5 days of hypocaloric peripheral parenteral nutrition. No significant modification was shown among control patients in CLAP (0.54 +/- 0.07 mL/min.kg-1 body wt vs 0.46 +/- 0.05 mL/min.kg-1 body wt in the preoperative period) or in antipyrine half-life (14.0 +/- 1.4 hours vs 16.5 +/- 1.8 hours). No significant correlation was observed between CLAP changes and those for the nutritional status of the patients. CONCLUSIONS: The results of our study indicate that oxidative drug-metabolizing capacity is increased in surgical patients maintained on hypocaloric peripheral parenteral nutrition. Clinicians should be conscious of the potential of this effect for altering the efficacy or toxicity of many therapeutic agents.