Biliary excretion of etoposide in children with cancer.
OBJECTIVE
Two children with soft tissue sarcomas receiving etoposide as part of their standard clinical treatment had external biliary drainage due to obstruction of the bile duct. These unusual cases provided an opportunity to investigate the biliary clearance of etoposide by determining etoposide concentrations in bile and plasma samples obtained during chemotherapy.


METHODS
Etoposide was administered to patient 1 at a dose of 150 mg/m(2), as a 4 h infusion, on each of three days of treatment. Patient 2 received a daily etoposide dose of 800 mg/m(2) as a 24 h continuous infusion, also over a 3-day treatment period. Bile and plasma samples were obtained at regular intervals from both patients and etoposide levels quantified by LC/MS analysis.


CONCLUSIONS
Biliary etoposide clearance was approximately equal to the flow of bile, with an average clearance of 0.32 ml/min determined in patient 1. Less than 2% of the etoposide dose administered was excreted in the bile in either patient studied, indicating that biliary clearance of etoposide is relatively minor. These results suggest that etoposide dose adjustment is unnecessary in patients with biliary obstruction.
Veal
Gareth J
GJ
Northern Institute for Cancer Research, Paul O'Gorman Building, Medical School, University of Newcastle upon Tyne, UK. G.J.Veal@newcastle.ac.uk
Errington
Julie
J
Thomas
Huw D
HD
Boddy
Alan V
AV
Lowis
Stephen
S
D000293:Adolescent; D000972:Antineoplastic Agents, Phytogenic / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001646:Bile / Q000378:metabolism*; D002675:Child, Preschool; D004322:Drainage; D005047:Etoposide / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D012509:Sarcoma / Q000188:drug therapy* / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D005047:Etoposide