Etoposide kinetics in patients with obstructive jaundice.
The kinetics and urinary excretion of etoposide and etoposide glucuronide were determined in 11 patients with obstructive jaundice (bilirubin greater than 2.0 mg/dL) and in 23 patients with normal renal and hepatic function. Mean (+/- SE) measurements of clearance (24.5 +/- 2.06 v 26.5 +/- 2.05 mL/min/m2), half-life (5.7 +/- 0.5 v 6.4 +/- 0.5 hours), and volume of distribution (12.4 +/- 1.1 v 13.7 +/- 1.6 L/m2) were not significantly different in patients with jaundice when compared with controls. Similarly, etoposide kinetics in three patients determined during a period of hyperbilirubinemia were not different from measurements made in the same patients following resolution of their obstructive jaundice. In patients with jaundice, 46% of an administered etoposide dose was excreted in the urine as etoposide compared with 35% in controls (P = .15). Urinary excretion of etoposide glucuronide accounted for 29% of an administered etoposide dose in control patients and 15% in those with hepatic obstruction (P = .03). Biliary etoposide excretion measured in four patients with T-tubes was insignificant (less than 2.0% of an administered dose). The calculated renal clearance of etoposide was 11.5 mL/min/m2 in patients with jaundice and 10.4 mL/min/m2 in controls (P = .53). Respective metabolic clearance was 4.9 and 6.9 mL/min/m2 in these two study groups (P = .13). Although hepatic metabolism of etoposide may be slightly decreased in patients with obstructive jaundice, a modest increase in renal etoposide excretion appears to compensate for this change, so that total clearance is similar in the patients with jaundice when compared with controls. No etoposide dose reductions appear to be needed in treating patients with obstructive jaundice who have normal renal function.
Hande
K R
KR
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.
Wolff
S N
SN
Greco
F A
FA
Hainsworth
J D
JD
Reed
G
G
Johnson
D H
DH
D001659:Biliary Tract / Q000378:metabolism; D002779:Cholestasis / Q000378:metabolism*; D001651:Cholestasis, Extrahepatic / Q000378:metabolism; D005047:Etoposide / Q000031:analogs & derivatives / Q000493:pharmacokinetics* / Q000652:urine; D006207:Half-Life; D006801:Humans; D006932:Hyperbilirubinemia / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism
C064401:etoposide glucuronide; D005047:Etoposide