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This study evaluates the metabolism of the anticancer drug topotecan (TPT) in the isolated perfused rat liver of male Wistar-rats. Using a sensitive high-performance liquid chromatography method, in bile TPT, its ring-opened hydroxycarboxylate form and three new metabolites could be quantified. Enzymatic hydrolysis of the metabolites with beta-glucuronidase and mass spectroscopy revealed the existence of glucuronidated TPT as well as unconjugated and glucuronidated bidesmethyl TPT. Biliary secretion of glucuronidated N-bidesmethyl TPT was fast reaching a maximum already after 15 min(30.6 +/- 15.1 pmol/g liver.min), whereas secretion of TPT, topotecan glucuronide and N-bidesmethyl TPT was delayed (maximum at 30 min: 431 +/- 19, 6.4 +/- 2.1 and 12.7 +/- 2.7 pmol/g liver.min, respectively). No release of TPT metabolites into the perfusate was detected. The amount of TPT, TPT glucuronide, N-bidesmethyl TPT and N-bidesmethyl TPT glucuronide excreted into bile during 60 min of perfusion was 2.10 +/- 0.483%, 0.031 +/- 0.006%, 0.058 +/- 0.013% and 0.108 +/- 0.012% of TPT cleared from the perfusate over 60 min, respectively. In conclusion we could identify three novel TPT metabolites, however, their overall metabolism in the rat liver is low.
P Platzer, and
S Schaden, and
T Thalhammer, and
G Hamilton, and
B Rosenberg, and
I Silgoner, and
W Jäger
January 1992,
Yao xue xue bao = Acta pharmaceutica Sinica,
P Platzer, and
S Schaden, and
T Thalhammer, and
G Hamilton, and
B Rosenberg, and
I Silgoner, and
W Jäger
January 1990,
Yao xue xue bao = Acta pharmaceutica Sinica,
P Platzer, and
S Schaden, and
T Thalhammer, and
G Hamilton, and
B Rosenberg, and
I Silgoner, and
W Jäger
January 1978,
Biochemical pharmacology,
P Platzer, and
S Schaden, and
T Thalhammer, and
G Hamilton, and
B Rosenberg, and
I Silgoner, and
W Jäger
January 1963,
Biochemische Zeitschrift,
P Platzer, and
S Schaden, and
T Thalhammer, and
G Hamilton, and
B Rosenberg, and
I Silgoner, and
W Jäger
January 1980,
Xenobiotica; the fate of foreign compounds in biological systems,
P Platzer, and
S Schaden, and
T Thalhammer, and
G Hamilton, and
B Rosenberg, and
I Silgoner, and
W Jäger
January 1999,
Acta medica (Hradec Kralove),
P Platzer, and
S Schaden, and
T Thalhammer, and
G Hamilton, and
B Rosenberg, and
I Silgoner, and
W Jäger
September 1985,
Mycotoxin research,
P Platzer, and
S Schaden, and
T Thalhammer, and
G Hamilton, and
B Rosenberg, and
I Silgoner, and
W Jäger
January 1993,
Drug metabolism and disposition: the biological fate of chemicals,
P Platzer, and
S Schaden, and
T Thalhammer, and
G Hamilton, and
B Rosenberg, and
I Silgoner, and
W Jäger
January 1977,
Drug metabolism and disposition: the biological fate of chemicals,
P Platzer, and
S Schaden, and
T Thalhammer, and
G Hamilton, and
B Rosenberg, and
I Silgoner, and
W Jäger
September 1976,
Research communications in chemical pathology and pharmacology,
