TY - JOUR
T1 - Altered pharmacokinetics and metabolism of CPT-11 in liver dysfunction
T2 - A need for guidelines
AU - Van Groeningen, C. J.
AU - Van Der Vijgh, W. J F
AU - Baars, J. J.
AU - Stieltjes, H.
AU - Huibregtse, K.
AU - Pinedo, H. M.
PY - 2000/4
Y1 - 2000/4
N2 - Metabolic conversion of CPT-11 is a major route of elimination of this new topoisomerase 1 inhibitor. Presently, recommendations for dose adjustments of CPT-11 in patients with liver dysfunction are lacking. We describe the case of a patient with metastatic colon cancer with liver dysfunction treated with CPT-11 at two different dose levels (100 mg/m2 and 30 mg/m2, single dose, administered as a 90-min i.v. infusion). The lactones and carboxylates of CPT-11 and SN-38 were determined by high-performance liquid chromatography. SN-38 glucuronide was determined after deglucuronidation. The procedures allowed intrapatient comparison of pharmacokinetics and metabolism of the drug. Severe side effects were encountered, which could be explained by the reduced clearance of CPT-11 and its metabolites. These included neutropenic fever with culture-proven septicemia, thrombocytopenia, somnolence, diarrhea, and signs and symptoms of transient hepatic failure. Our findings offer important data for the further development of guidelines for dose reduction of CPT-11 in patients with liver dysfunction.
AB - Metabolic conversion of CPT-11 is a major route of elimination of this new topoisomerase 1 inhibitor. Presently, recommendations for dose adjustments of CPT-11 in patients with liver dysfunction are lacking. We describe the case of a patient with metastatic colon cancer with liver dysfunction treated with CPT-11 at two different dose levels (100 mg/m2 and 30 mg/m2, single dose, administered as a 90-min i.v. infusion). The lactones and carboxylates of CPT-11 and SN-38 were determined by high-performance liquid chromatography. SN-38 glucuronide was determined after deglucuronidation. The procedures allowed intrapatient comparison of pharmacokinetics and metabolism of the drug. Severe side effects were encountered, which could be explained by the reduced clearance of CPT-11 and its metabolites. These included neutropenic fever with culture-proven septicemia, thrombocytopenia, somnolence, diarrhea, and signs and symptoms of transient hepatic failure. Our findings offer important data for the further development of guidelines for dose reduction of CPT-11 in patients with liver dysfunction.
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M3 - Article
C2 - 10778961
AN - SCOPUS:0034006699
SN - 1078-0432
VL - 6
SP - 1342
EP - 1346
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 4
ER -