Document Detail


Severe CPT-11-induced diarrhea in presence of FK-506 following liver transplantation for hepatocellular carcinoma.
MedLine Citation:
PMID:  11911319     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. PATIENT AND 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. CONCLUSION: The starting dose of CPT-11 should be reduced in FK506-treated liver transplant patients.
Authors:
J M Gornet; F Lokiec; J C Duclos-Vallee; D Azoulay; F Goldwasser
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Publication Detail:
Type:  Case Reports; Journal Article    
Journal Detail:
Title:  Anticancer research     Volume:  21     ISSN:  0250-7005     ISO Abbreviation:  Anticancer Res.     Publication Date:    2001 Nov-Dec
Date Detail:
Created Date:  2002-03-25     Completed Date:  2002-04-19     Revised Date:  2007-09-25    
Medline Journal Info:
Nlm Unique ID:  8102988     Medline TA:  Anticancer Res     Country:  Greece    
Other Details:
Languages:  eng     Pagination:  4203-6     Citation Subset:  IM    
Affiliation:
Service de Cancérologie, Hôpital Paul Brousse, AP-HP, Villejuif, France.
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MeSH Terms
Descriptor/Qualifier:
Adult
Antineoplastic Agents, Phytogenic / adverse effects*,  blood,  pharmacokinetics
Camptothecin / adverse effects*,  analogs & derivatives*,  blood,  pharmacokinetics
Diarrhea / chemically induced*
Drug Interactions
Glucuronides / blood,  pharmacokinetics
Humans
Liver Transplantation*
Tacrolimus / adverse effects*,  blood,  pharmacology
Chemical
Reg. No./Substance:
0/7-ethyl-10-hydroxycamptothecin glucuronide; 0/Antineoplastic Agents, Phytogenic; 0/Glucuronides; 100286-90-6/irinotecan; 109581-93-3/Tacrolimus; 7689-03-4/Camptothecin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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