Pharmacokinetics and toxicity of irinotecan hydrochloride: effects of polymorphisms in transporter genes
- Conditions
- malignant solid tumor (pancreatic cancer, colorectal cancer, gastric cancer, lung cancer, ovarian cancer,breast cancer, neuroendocrine carcinoma)
- Registration Number
- JPRN-UMIN000023783
- Lead Sponsor
- Showa university school of medicine
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- All
- Target Recruitment
- 100
Not provided
1) Severe active infection. 2) Sever diarrhea. 3) Gastrointestinal paresthesia and bowel obstruction. 4) Interstitial pneumonia, pulmonary fibrosis. 5) Jaundice. 6) Patient who need drainage of peritoneal, pleural or pericardial effusion. 7) Unstable angina, myocardial infarction or heart failure within 3 months. 8) Severe complication (e.g., uncontrollable diabetis mellitus, liver disease). 9) Serological positive for HBs-antigen or HCV-antibody. 10) Intestinal resection within 4 weeks prior to enrollment or colostomy within 2 weeks prior to enrollment. 11) Patients who received chemotherapy not to include irinotecan hydrochloride, or radiation therapy within two weeks. 12) Severe hypersensitivity to medicine. 13) Patients who has difficulty in getting the understanding for the study. 14) Pregnant or lactating women, or men and women without wanting pregnancy. 15) Patients who were judged inappropriate for the study.
Study & Design
- Study Type
- Observational
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method We analyze genetic polymorphism of OATP1B1, ABCG2 and OATP2B1 and Pharmacokinetics/Pharmacodynamics of the irinotecan and metabolite and toxicity expression relations of the irinotecan hydrochloride.
- Secondary Outcome Measures
Name Time Method (1) We analyze about genetic polymorphism(OATP1B3, ABCB1, ABCC2 and CES2 which participates in activation of irinotecan, CYP3A4 which participates in inactivation of irinotecan) and a relation between PK/PD and toxicity. (2) We analyze the genetic seasonal polymorphism to encode microRNA (miRNA) and the genetic polymorphism of an enzyme participating in processing of miRNA and PK/PD of the irinotecan hydrochloride and relations with the toxicity. (3) We measure the plasma concentration of an internal compound becoming the OATP substrate and evaluate OATP inhibition by SN-38 and get grounds to estimate the interaction risk between the drug in the irinotecan hydrochloride dosage. (4) We perform meta genome analysis of the enterobacterial flora and analyze a relation between toxicity of irinotecan hydrochloride (including the diarrhea) and enterobacterial flora.