| pubmed-article:7264895 | pubmed:abstractText | The urinary excretion and blood level kinetics of p-methylbenzoylformic acid (I) after intravenous infusion for 1 hr were studied in rats. The determined first-order half-lives were compared with those determined in studies in which a single intravenous dose of I was administered rapidly to rts that previously were infused with normal saline for 1 hr. While the blood t 1/2 or body clearance of I determined in the 1-hr infusion studies was similar to that determined in the single intravenous dose studies, the urinary of t 1/2 of I determined in the 1-hr infusion studies was significantly greater than that determined in the single intravenous dose studies. In infusion studies where the half-lives of I were determined in the presence of renal tubular secretion inhibitor, DL-tropic acid (II), the ratio of (urinary t 1/2)II present/(urinary t 1/2)II absent was almost twice the ratio of (blood t 1/2)II present/(blood t 1/2)II absent. The urinary t 1/2 value of I determined after infusion for only 10 min was intermediate between values obtained in the single intravenous dose studies and the 1-hr infusion studies. These data provide pharmacokinetic evidence to support the hypothesis that I and other organic anions temporarily accumulate in the surface-lying renal tubular cells after a single intravenous dose, but they tend to penetrate into the deeper renal tubular cells upon intravenous infusion, with depth of penetration increasing with increasing infusion time. | lld:pubmed |
