Interaction of buspirone and its major metabolites with human organic cation transporters
3
Issued Date
2023-01-01
Resource Type
ISSN
07673981
eISSN
14728206
Scopus ID
2-s2.0-85149466479
Pubmed ID
36843181
Journal Title
Fundamental and Clinical Pharmacology
Rights Holder(s)
SCOPUS
Bibliographic Citation
Fundamental and Clinical Pharmacology (2023)
Suggested Citation
Jinakote M., Jutabha P., Anzai N., Ontawong A., Soodvilai S., Inchai J., Vaddhanaphuti C.S. Interaction of buspirone and its major metabolites with human organic cation transporters. Fundamental and Clinical Pharmacology (2023). doi:10.1111/fcp.12883 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/82226
Title
Interaction of buspirone and its major metabolites with human organic cation transporters
Other Contributor(s)
Abstract
Buspirone, a cationic drug, is an anxiolytic and antidepressant drug. However, whether buspirone and its metabolites are interacted with organic cationic transporter remains uncertain. In this study, we examined the interaction of buspirone and its major metabolites 1-(2-pyrimidinyl)piperazine (1-PP) and 6-hydroxybuspirone (6′-OH-Bu) with hOCTs using human hepatocellular carcinoma (HepG2), human colorectal adenocarcinoma (Caco-2) cells, and S2 cells expressing OCT1 (S2hOCT1), 2 (S2hOCT2), or 3 (S2hOCT3). Coadministration of buspirone and fluorescent 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP+) was examined using HepG2 cells, and [3H]-1-methyl-4-phenylpyridinium (MPP+) transport was assessed in S2 cell overexpressing hOCTs. The results showed that ASP+ transport was suppressed by buspirone with an IC50 of 26.3 ± 2.9 μM without any cytotoxic effects in HepG2 expressing hOCTs cells. Consistently, buspirone strongly inhibited [3H]-MPP+ uptake by S2hOCT1, S2hOCT2, and S2hOCT3 cells with an IC50s of 89.0 ± 1.3 μM, 43.7 ± 7.5 μM, and 20.4 ± 1.0 μM, respectively. Nonetheless, 6′-OH-Bu and 1-PP caused weak or no inhibition on ASP+ and [3H]-MPP+ transport. These findings suggest the potential interaction of buspirone with organic cation drugs that are handled by hOCT3. However, further clinical relevance is needed to support these findings for preventing drug–drug interaction in patients who take prescribed drugs together with buspirone.