title: Metabolic studies of a podophyllotoxin derivative (VP16) in the isolated perfused liver.
abstract: The metabolism of VP16 was studied in isolated perfused rat liver. The rate of elimination into the medium and excretion in bile were determined by h.p.l.c. with u.v. detection. With high VP16 concentrations (180 micrograms/ml medium), the elimination half-life of the compound was prolonged markedly (156 v. 45 min for lower doses), the percentage recovered in bile was more than halved and drug accumulation in the hepatic tissue was three times greater. These findings indicate saturation of metabolism and of biliary elimination during high-dose treatment. The presence of glucuronides in the bile of VP16 perfused livers indicates that VP16 undergoes conjugation with glucuronic acid. Formation of picro isomer of VP16 in the liver also occurs.
mesh_terms: D000818:Animals; D001646:Bile / Q000032:analysis; D005047:Etoposide / Q000378:metabolism*; D066298:In Vitro Techniques; D007536:Isomerism; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D010477:Perfusion; D011034:Podophyllotoxin / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
chemical_list: D005047:Etoposide; D011034:Podophyllotoxin