Age dependent differences in the pharmacokinetics of furosemide in rats

: After i.p. administration of 0,60 mg/100 g of furosemide, adult rats excreted 50 to 70% of this diuretic drug unchanged and 10% as desfurylmethylfurosemide. The renal excretion of furosemide is slower in 5- and 15-day-old rats. Age differences in absorption from the abdominal cavity or in the reabsorption rate in the kidney tubules can be excluded. The excretion of furosemide by the kidney is competitively inhibited by p-aminohippuric acid (PAH). The relative small inhibitory effect of PAH in young rats is caused by a smaller participation of tubular secretion in the renal excretion of furosemide in this age group. The half life time of furosemide is 83 min in 5-day-old rats and 47 min in 55-day-old rats. The distribution volume is 146% of body weight in both age groups. The concentration of furosemide in the kidney homogenate is higher in young rats than in adults. The slow renal excretion of furosemide in young rats is in accordance with the prolonged efficacy. The greater efficacy of furosemide in 5- and 15-day-old rats than in adults is caused particularly by differences in the conditions for diuretic effectiveness, especially by the retention of water and electrolytes in young rats.