KIDNEY METABOLISM OF ACETAMINOPHEN AND PHENACETIN

  • 1 January 1978
    • journal article
    • research article
    • Vol. 92  (6) , 924-931
Abstract
The metabolism of acetaminophen and phenacetin by rabbit kidney slices was investigated. Phenacetin, like aspirin, inhibited [13I] Hippuran accumulation by the organic acid transport system. Phenacetin exhibited a dose-dependent inhibition with a KI [inhibition constant] of 0.5 mM; acetaminophen at concentrations are high as 1 mM did not alter organic acid transport. [3H] acetaminophen slice: media ratios of approximately 1 or less suggested that acetaminophen entered cortex and outer and inner medullary slices by diffusion rather than active transport. Approximately 95% of the acetaminophen within the slices readily diffused out into the media. The chromatographic patterns of this material were similar to that of the incubation media. The acetaminophen remaining within the slices was acid-precipitable and not extractable with organic solvents. This covalent binding of acetaminophen was inhibited by glutathione. More acetaminophen was bound in the renal medulla than cortex. The renal metabolism of acetaminophen observed in this in vitro study may be related to the nephritis observed in analgesic abuse.