Brief Report: High Peak Level of Plasma Raltegravir Concentration in Patients With ABCB1 and ABCG2 Genetic Variants.
Raltegravir was recently identified to be a substrate of ATP-binding cassette transporter B1 (ABCB1) and G2 (ABCG2), which are efflux transporters and expressed in the intestines. We analyzed the relations between plasma raltegravir concentrations and single nucleotide polymorphism of ABCB1 and ABCG2 genes. The peak plasma concentration of raltegravir was significantly higher in the patients with ABCB1 4036 AG/GG and ABCG2 421 CA/AA than in other genotype holders (P = 0.0052), though no difference was identified in trough raltegravir concentrations, which may be explained by reduced expression of efflux transporters in intestine by these genetic variants.
*AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan;†Department of Clinical Pharmacology, Group for Translational Research Support Core, National Cancer Center Research Institute, Tokyo, Japan;‡Department of Medical Oncology and Translational Research, Kumamoto University, Kumamoto, Japan; and§Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
Kiyoto
K
Tsuchiya
Tsunefusa
T
Hayashida
Akinobu
A
Hamada
Shinichi
S
Oka
Hiroyuki
H
Gatanaga
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D004359:Drug Therapy, Combination; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D019428:HIV Integrase Inhibitors / Q000097:blood* / Q000627:therapeutic use; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D000068898:Raltegravir Potassium / Q000097:blood* / Q000627:therapeutic use; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use
C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D019428:HIV Integrase Inhibitors; D009363:Neoplasm Proteins; D018894:Reverse Transcriptase Inhibitors; D000068898:Raltegravir Potassium