Investigation of UGT1A1 Polymorphism and Pharmacokinetic Analysis on Irinotecan (CPT-11) and its Metabolites for a Patient Who Developed Severe Neutropenia during Treatment with IFL Regimen

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  • ＩＦＬ療法によりｇｒａｄｅ　４の好中球減少が認められた大腸がん患者のＵＧＴ１Ａ１遺伝子多型と薬物体内動態解析

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We carried out a pharmacogenetic analysis on uridine diphosphate glucuronosyltransferase (UGT)1A1 polymorphism and a pharmacokinetic analysis on irinotecan (CPT-11)and its metabolites for a patient who developed severe neutropenia after the first course of a CPT-11 (100 mg/m2),5-fluorouracil (5-FU) and leucovorin regimen (IFL regimen).Genotyping showed the patient to be homozygous for the UGT1A1*28 allele and heterozygous for UGT1A1*27 allele.In the pharmacokinetic analysis,the serum concentrations of CPT-11,SN-38,SN-38 glucuronide and 5-FU were measured.<br>The AUC0-23.25h of SN-38 was 523.6 ng·h/mL at a dose of 32.5 mg/m2 of CPT-11,which was higher than that in the literature at a dose of 100 mg/m2.The serum concentration of 5-FU,however,was lower than that in the literature for the same dose.Lowering the dose of CPT-11 from 100 to 26 mg/m2 resulted in a decrease in CEA and CA 19-9 concentrations and a reduction in the lung metastatic focus.Considered together with the change in absolute neutrophil count observed,these findings suggested that the doses of CPT-11,5-FU and L-leucovorin be adjusted to 26 mg/m2,324 mg/m2 and 195 mg/m2 respectively and the washout period be extended.<br>In conclusion,the UGT1A1 genetic analysis and follow-up monitoring of serum CPT-11 levels that we conducted facilitated the creation of a personalized IFL regimen for the patient,which improved efficacy and safety.

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