Severe CPT-11-induced diarrhea in presence of FK-506 following liver transplantation for hepatocellular carcinoma.
BACKGROUND
The treatment of malignancies in transplanted patients has become an emerging issue. The anticancer agent CPT-11 is hydrolysed to the active metabolite SN-38 and many drugs interact with its metabolism and toxicity.


METHODS
We studied the clinical and pharmacological interactions between CPT-11 and FK506 in a liver transplant patient. Serial plasma samples of FK506, CPT-11, SN-38 and SN-38 glucuronide were assayed by high-performance liquid chromatography.


RESULTS
While no CPT-11 toxicity was observed pre-operatively, several post-operative cycles of CPT-11 were complicated with severe diarrhea. No change in FK506 plasma concentrations was noted in the presence of CPT-11 but the pharmacokinetics of CPT-11 was altered in the presence of FK506. SN-38 glucuronidation was reduced for up to 12 hours following CPT-11 infusion. This increase in plasmatic exposure to unbound SN-38 might account for diarrhea.


CONCLUSIONS
The starting dose of CPT-11 should be reduced in FK506-treated liver transplant patients.
Gornet
J M
JM
Service de Cancérologie, Hôpital Paul Brousse, AP-HP, Villejuif, France.
Lokiec
F
F
Duclos-Vallee
J C
JC
Azoulay
D
D
Goldwasser
F
F
D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects* / Q000097:blood / Q000493:pharmacokinetics; D002166:Camptothecin / Q000009:adverse effects* / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics; D003967:Diarrhea / Q000139:chemically induced*; D004347:Drug Interactions; D020719:Glucuronides / Q000097:blood / Q000493:pharmacokinetics; D006801:Humans; D000077146:Irinotecan; D016031:Liver Transplantation; D016559:Tacrolimus / Q000009:adverse effects* / Q000097:blood / Q000494:pharmacology
C441475:7-ethyl-10-hydroxycamptothecin glucuronide; D000972:Antineoplastic Agents, Phytogenic; D020719:Glucuronides; D000077146:Irinotecan; D016559:Tacrolimus; D002166:Camptothecin