Relation between renal and hepatic excretion of drugs. XIV. Elimination of ioglycamic acid after nephrectomy, bile duct ligation, and after treatment with hormones or xenobiotics in young and adult rats.
Ioglycamic acid (IGA) is effectively eliminated in young and adult rats via urine and bile. After administration of low doses hepatic excretion dominates whereas following high supply renal elimination surpasses biliary excretion. Hepatic transport of IGA is active, indicated by the occurrence of a transport maximum in vivo and by a distinct accumulation of this drug within liver slices in vitro. Renal removal of IGA is preferentially caused by glomerular filtration. A tubular reabsorption obviously does not occur because forced diuresis (mannitol, furosemide) does not increase renal excretion of this substance. As calculated from our clearance data and as a result of accumulation experiments in vitro on renal cortical slices the active tubular secretion of this organic anion can be excluded. In principle there are no qualitative changes in IGA elimination between the 20th and 55th day of life, but active hepatic transport of the drug is significantly lower in young, immature rats. After bile duct ligation, renal excretion of IGA increases distinctly in both age groups, whereas in adult rats bilateral nephrectomy (NX) is followed by a significant decrease in its hepatic excretion in dependence on time after kidney removal. In young rats NX is without consequences on hepatic excretion of IGA. It is possible to stimulate renal and/or hepatic excretion of IGA by repeated administration of T3, dexamethasone, or phenobarbital. The effect of stimulation is different in kidney and liver and depends on age, too.
Fleck
C
C
Friedrich Schiller University, Institute of Pharmacology and Toxicology, Jena, Germany.
Kabath
P
P
Linstedt
A
A
Linstedt
U
U
Scharke
U
U
Bräunlich
H
H
D000818:Animals; D001652:Bile Ducts / Q000601:surgery; D003518:Cyclopenthiazide / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D007471:Ioglycamic Acid / Q000493:pharmacokinetics*; D007668:Kidney / Q000378:metabolism*; D008026:Ligation; D008099:Liver / Q000378:metabolism*; D009392:Nephrectomy; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014284:Triiodothyronine / Q000494:pharmacology
D014284:Triiodothyronine; D003907:Dexamethasone; D007471:Ioglycamic Acid; D003518:Cyclopenthiazide; D010634:Phenobarbital