The effect of age on antipyrine pharmacokinetics and metabolite formation in rats

The great interindividual variation in drug handling, especially in the elderly, causes a problem in determining the correct individual dose for the administration of a drug. A solution would be the determination of the capacity to metabolize lipophilic drugs in vivo on an individual basis. One approach, as reported in the literature, may be to determine the clearance rates of the antipyrine metabolites, which are formed by different isoenzymes of cytochrome P-450. Pharmacokinetics of antipyrine were determined in 3-, 12-, 24-, 30- and 36-month-old male BN/BiRij rats. The elimination T1/2 did not change with age, or were changes found in apparent volume of distribution. The systemic clearance of 24-month-old rats, when expressed as milliliters per minute-1 was higher than that of 3- and 12-month-old ones. When expressed as milliliters per minute-1 per kilogram-1, the systemic clearance decreased between 3 and 12 months. Thereafter, no change occurred. The partial clearance, expressed as milliliters per minute-1, did not change with age. Expressed as milliliters per minute-1 per kilogram-1, the partial clearance of the metabolites also did not change for hydroxymethylantipyrine (HMA) and 4-hydroxyantipyrine (4-OHA) but for norantipyrine (NORA) a decrease was found between 3 and 24 months, followed by a tendency to increase between 24 and 36 months. When the data were expressed per rat (milliliters per minute-1), the increase in liver weight with age influenced the data markedly.(ABSTRACT TRUNCATED AT 250 WORDS)