SEX-DEPENDENT AND INDEPENDENT RENAL EXCRETION OF NILVADIPINE METABOLITES IN RAT - EVIDENCE FOR A SEX-DEPENDENT ACTIVE SECRETION IN KIDNEY

1. To clarify the mechanism of sex-dependent and independent kidney se cretion of major nilvadipine metabolites (3, 7) in rat, renal clearanc e corrected for protein binding and glomerular filtration rate (GFR) w as measured in both sexes. The effect of probenecid, an inhibitor of o rganic anion transport, on these measurements was also investigated. 2 . Clear sex-dependent active secretion was observed in the renal excre tion of 3 (3-carboxylic acid pyridine derivative). In the female rat, 3, clearance was approximately 32-fold greater than GFR and was marked ly decreased by probenecid. Conversely, in the male rat, renal clearan ce of 3 was only a fraction of GFR and was unaffected by probenecid. 3 . Sex-independent active secretion was observed in the renal excretion of 7 (5-carboxylic acid pyridine derivative). In both sexes of rat 7 clearance was about 22-fold greater than GFR and was markedly reduced by probenecid. 4. A clear presence of sex-dependent and independent ac tive secretion mechanisms in the kidney has been demonstrated in rat. The female rat is able to eliminate 3 and 7 in urine by an active secr etion mechanism that is inhibited by probenecid. In the male rat, a tr ansport mechanism for 7 is present, but either lacks or is apparently inactive for 3.