Interaction of renal excretion between nilvadipine metabolites, M3 and M7 in rats: characterization of sex-dependent and sex-independent active secretion in the kidney.
The interaction of renal clearance between nilvadipine metabolites, M3 and M7, in male and female rats including protein binding and renal excretion was investigated to clarify the mechanisms involved. In male rats, active renal secretion of M7 (the 5-carboxylic acid pyridine derivative) was reduced in inverse proportion to the molar ratio of the plasma concentration M3/M7 after an i.v. dose of M3 (the 3-carboxylic acid pyridine derivative), and the dosed M3 was excreted only by glomerular filtration. In female rats, the active renal secretion of M7 was unaffected after an i.v. dose of M3, and the dosed M3 was excreted by active secretion. These results indicate an interference of the active secretion of M7 in male rats by M3 on competitive interaction at the renal tubular secretion, even though M3 was excreted only via a filtration process. Female rats may have two distinct and separate active renal secretion mechanisms for M7 and M3, even though these carboxylic acid compounds were eliminated by active transport in the kidney.
Terashita
S
S
Product Development Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, Osaka, Japan.
Sawamoto
T
T
Tozuka
Z
Z
Tokuma
Y
Y
Hata
T
T
D000818:Animals; D001693:Biological Transport, Active; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000493:pharmacokinetics*; D004347:Drug Interactions; D005260:Female; D005919:Glomerular Filtration Rate; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D007668:Kidney / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics
D002121:Calcium Channel Blockers; C035100:nilvadipine; D009543:Nifedipine