title: Circulating intestine-derived exosomal miR-328 in plasma, a possible biomarker for estimating BCRP function in the human intestines.
abstract: A variant in the breast cancer resistance protein (BCRP) gene, 421C> A is a useful biomarker for describing large inter-individual differences in the pharmacokinetics of sulfasalazine (SASP), a BCRP substrate. However, large intra-genotypic variability still exists in spite of the incorporation of this variant into the pharmacokinetics of SASP. Since miR-328 negatively regulates BCRP expression in human tissues, we hypothesized that exosomal miR-328 in plasma, which leaks from the intestines, is a possible biomarker for estimating BCRP activity in the human intestines. We established an immunoprecipitation-based quantitative method for circulating intestine-derived miR-328 in plasma using an anti-glycoprotein A33 antibody. A clinical study was conducted with an open-label, non-randomized, and single-arm design involving 33 healthy participants. Intestine-derived exosomal miR-328 levels positively correlated (P < 0.05) with SASP AUC0-48, suggesting that subjects with high miR-328 levels have low intestinal BCRP activity, resulting in the high AUC of SASP. Circulating intestine-derived exosomal miR-328 in plasma has potential as a possible biomarker for estimating BCRP function in the human intestines.
authors: Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors: Keisuke
authors: K
authors: Gotanda
authors: Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors: Takeshi
authors: T
authors: Hirota
authors: Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors: Jumpei
authors: J
authors: Saito
authors: Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors: Masato
authors: M
authors: Fukae
authors: Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors: Yu
authors: Y
authors: Egashira
authors: SOUSEIKAI Global Clinical Research Center, Fukuoka, Japan.
authors: Noritomo
authors: N
authors: Izumi
authors: SOUSEIKAI Global Clinical Research Center, Fukuoka, Japan.
authors: Mariko
authors: M
authors: Deguchi
authors: SOUSEIKAI Global Clinical Research Center, Fukuoka, Japan.
authors: Miyuki
authors: M
authors: Kimura
authors: SOUSEIKAI Global Clinical Research Center, Fukuoka, Japan.
authors: Shunji
authors: S
authors: Matsuki
authors: SOUSEIKAI Global Clinical Research Center, Fukuoka, Japan.
authors: Shin
authors: S
authors: Irie
authors: Department of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors: Ichiro
authors: I
authors: Ieiri
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2 / Q000235:genetics* / Q000378:metabolism; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D055354:Exosomes / Q000235:genetics* / Q000648:ultrastructure; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D035683:MicroRNAs / Q000097:blood / Q000235:genetics*; D046529:Microscopy, Electron, Transmission; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D012460:Sulfasalazine / Q000097:blood / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D000890:Anti-Infective Agents; D015415:Biomarkers; C548170:MIRN328 microRNA, human; D035683:MicroRNAs; D009363:Neoplasm Proteins; D012460:Sulfasalazine; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human