Additive effects of drug transporter genetic polymorphisms on irinotecan pharmacokinetics/pharmacodynamics in Japanese cancer patients
Copyright policy )Additive effects of drug transporter genetic polymorphisms on irinotecan pharmacokinetics/pharmacodynamics in Japanese cancer patients
Effects of genetic polymorphisms/variations of ABCB1, ABCC2, ABCG2 and SLCO1B1 in addition to "UGT1A1*28 or *6" on irinotecan pharmacokinetics/pharmacodynamics in Japanese cancer patients were investigated.Associations between transporter haplotypes/variations along with UGT1A1*28 or *6 and SN-38 area under the time-concentration curve (AUC) or neutropenia were examined in irinotecan monotherapy (55 patients) and irinotecan-cisplatin-combination therapy (62 patients).Higher SN-38 AUC values were observed in ABCB1 2677G>T (A893S) (*2 group) for both regimens. Associations of grade 3/4 neutropenia were observed with ABCC2 -1774delG (*1A), ABCG2 421C>A (Q141K) and IVS12 + 49G>T ((#) IIB) and SLCO1B1 521T>C (V174A) (*15 x 17) in the irinotecan monotherapy, while they were evident only in homozygotes of ABCB1*2, ABCG2 (#) IIB, SLCO1B1*15 x 17 in the cisplatin-combination therapy. With combinations of haplotypes/variations of two or more genes, neutropenia incidence increased, but their prediction power for grade 3/4 neutropenia is still unsatisfactory.Certain transporter genotypes additively increased irinotecan-induced neutropenia, but their clinical importance should be further elucidated.
- Kobe University Japan
- National Institute of Health Sciences Japan
- Kobe University Hospital Japan
- National Cancer Research Institute United Kingdom
- National Cancer Center Hospital Korea (Republic of)
Neutropenia, Genotype, Organic Anion Transporters, Irinotecan, Polymorphism, Single Nucleotide, Multidrug Resistance-Associated Protein 2, Asian People, Haplotypes, Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Humans, Camptothecin, Cisplatin, Glucuronosyltransferase
Neutropenia, Genotype, Organic Anion Transporters, Irinotecan, Polymorphism, Single Nucleotide, Multidrug Resistance-Associated Protein 2, Asian People, Haplotypes, Neoplasms, Antineoplastic Combined Chemotherapy Protocols, Humans, Camptothecin, Cisplatin, Glucuronosyltransferase
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