Age dependent differences in stimulation and compensation of renal and biliary transport processes. Correlation to the physicochemical properties of the exerted substances.
The relation between renal and biliary excretion of drugs was investigated in dependence on physicochemical factors, on age, and on repeated administration of hormones and xenobiotics for stimulation. Furthermore, the relation between molecular parameters of drugs and the degree of compensation of drug elimination after blockade of one excretion pathway (nephrectomy--NX, bile duct ligation--DL) was characterized. Experiments were performed on female 20-day and 55-day-old rats to demonstrate changes in the relationship between kidney and liver for drug elimination during ontogenesis. Finally it was tried to correlate the effect of a stimulation of elimination capacity of kidney and liver after repeated administration of hormones or xenobiotics and the physicochemical features of clearance substances tested. For estimation of physicochemical differences of the model substances a so called "rank coefficient" R (0-100) was used. It was calculated from molecular weight, lipophilicity, degree of ionization at pH 7.4, and protein binding rate. Compounds with low ranks (low values of molecular weight, lipophilicity, and protein binding, nearly completely ionic at pH 7.4) are eliminated first of all via urine. High ranks are typical of drugs preferentially eliminated into bile. Intermediate ranks (40-60) have been obtained for substances eliminated effectively both via kidney and liver. For these compounds only, a distinct compensation via the intact elimination route can be expected after blocking operations. Qualitative age differences could not be found. But there were differences concerning relation between acceleration of transport capacity of kidney and liver during postnatal maturation and physicochemical properties of the respective test substance.(ABSTRACT TRUNCATED AT 250 WORDS)
Fleck
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Institute of Pharmacology and Toxicology, Friedrich Schiller University, Jena, German Democratic Republic.
Bräunlich
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H
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000378:metabolism*; D001693:Biological Transport, Active; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004396:Coloring Agents; D003518:Cyclopenthiazide / Q000493:pharmacokinetics; D003907:Dexamethasone / Q000493:pharmacokinetics; D005260:Female; D007668:Kidney / Q000378:metabolism*; D008111:Liver Function Tests; D010634:Phenobarbital / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D014284:Triiodothyronine / Q000493:pharmacokinetics; D014325:Tromethamine / Q000493:pharmacokinetics
D004396:Coloring Agents; D014325:Tromethamine; D014284:Triiodothyronine; D003907:Dexamethasone; D003518:Cyclopenthiazide; D010634:Phenobarbital