In vitro digitoxin metabolism. Rate-limiting step and alteration following spironolactone pretreatment.
The biotransformation of digitoxin was considered as a linear transformation comprised of dual deoxy sugar cleavages culminating with product conjugation to glucuronic acid. Digitoxin and two metabolites, digitoxigenin bisdigitoxoside and digitoxigenin monodigitoxoside, were each incubated for 1 hr with rat liver slices. Measurements of amounts of various metabolites allowed determination of rate constants, showing the cleavage of the terminal sugar from digitoxigenin bisdigitoxoside to be the rate-limiting step. The inductive action of spironolactone predominately affected the rate-limiting step.
Kershaw
W C
WC
Campbell
P
P
Lage
G L
GL
D000818:Animals; D004073:Digitoxigenin / Q000378:metabolism; D004074:Digitoxin / Q000378:metabolism*; D006900:Hydroxylation; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013148:Spironolactone / Q000494:pharmacology*
D004073:Digitoxigenin; D013148:Spironolactone; D004074:Digitoxin