Impact of 1α,25-dihydroxyvitamin D3 on biodistribution and pharmacokinetics of L-carnitine and creatinine, organic cation/carnitine transporter 2 and organic cation transporter 2 biomarkers
DC Field | Value | Language |
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dc.contributor.author | Vo, Dang-Khoa | - |
dc.contributor.author | Nguyen, Thi-Thao-Linh | - |
dc.contributor.author | Maeng, Han-Joo | - |
dc.date.accessioned | 2024-05-01T10:30:20Z | - |
dc.date.available | 2024-05-01T10:30:20Z | - |
dc.date.issued | 2024-05 | - |
dc.identifier.issn | 2093-5552 | - |
dc.identifier.issn | 2093-6214 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/gachon/handle/2020.sw.gachon/91066 | - |
dc.description.abstract | Purpose This study investigated effects of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)(2)D-3] on biodistribution and pharmacokinetics of L-carnitine and creatinine as organic cation/carnitine transporter 2 (OCTN2) and organic cation transporter 2 (OCT2) biomarkers, respectively, together with mRNA expressional changes. Methods After four consecutive days of pretreatment with 1,25(OH)(2)D3 (2.56 nmol/kg/day), plasma, urine, and tissues were collected for analysis of endogenous L-carnitine and creatinine basal levels, or rats were intravenously administered exogenous L-carnitine (50 mg/kg). The selected tissues were subjected to analysis of rOCTN2 and rOCT2 gene expression using real-time quantitative polymerase chain reaction. The quantification of L-carnitine and creatinine was performed with liquid chromatography-tandem mass spectrometry. Results 1,25(OH)2D3-treated rats exhibited decreased rOCTN2 mRNA expression in the liver, kidney, spleen, and brain, and decreased rOCT2 mRNA expression in the kidney. L-carnitine levels indicated that basal plasma abundance in the 1,25(OH)(2)D-3-treated group elevated, whereas the tissue-plasma partition coefficient dropped in all tissues and the urine level also reduced. Exogenous L-carnitine pharmacokinetics were consistent with the endogenous level, with a significant rise in area under the curve and significant decreases in renal clearance and volume of distribution at steady state in the group treated with 1,25(OH)(2)D-3. Additionally, the significant increase in plasma levels and decrease in renal clearance of creatinine were likely due to decreased OCT2 function. Conclusion Our observations suggest the risk of co-administering 1,25(OH)(2)D-3 with OCT2 and/or OCTN2 substrates. Moreover, this study confirmed that L-carnitine and creatinine are sensitive endogenous biomarkers of OCTN2- and OCT2-mediated drug-drug interactions, respectively. | - |
dc.format.extent | 14 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | SPRINGERNATURE | - |
dc.title | Impact of 1α,25-dihydroxyvitamin D3 on biodistribution and pharmacokinetics of L-carnitine and creatinine, organic cation/carnitine transporter 2 and organic cation transporter 2 biomarkers | - |
dc.type | Article | - |
dc.identifier.wosid | 001158156400001 | - |
dc.identifier.doi | 10.1007/s40005-023-00659-2 | - |
dc.identifier.bibliographicCitation | JOURNAL OF PHARMACEUTICAL INVESTIGATION, v.54, no.3, pp 389 - 402 | - |
dc.identifier.kciid | ART003080683 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.scopusid | 2-s2.0-85184232502 | - |
dc.citation.endPage | 402 | - |
dc.citation.startPage | 389 | - |
dc.citation.title | JOURNAL OF PHARMACEUTICAL INVESTIGATION | - |
dc.citation.volume | 54 | - |
dc.citation.number | 3 | - |
dc.type.docType | Article | - |
dc.publisher.location | 영국 | - |
dc.subject.keywordAuthor | 1 alpha,25-dihydroxyvitamin D-3 | - |
dc.subject.keywordAuthor | OCTN2 | - |
dc.subject.keywordAuthor | OCT2 | - |
dc.subject.keywordAuthor | Endogenous biomarkers | - |
dc.subject.keywordAuthor | Pharmacokinetics | - |
dc.subject.keywordAuthor | Drug-drug interactions | - |
dc.subject.keywordPlus | VITAMIN-D-RECEPTOR | - |
dc.subject.keywordPlus | ACETYL-L-CARNITINE | - |
dc.subject.keywordPlus | SERUM CREATININE | - |
dc.subject.keywordPlus | ENDOGENOUS BIOMARKERS | - |
dc.subject.keywordPlus | RENAL CLEARANCE | - |
dc.subject.keywordPlus | OCTN2 SLC22A5 | - |
dc.subject.keywordPlus | D METABOLITES | - |
dc.subject.keywordPlus | RAT | - |
dc.subject.keywordPlus | PLASMA | - |
dc.subject.keywordPlus | DEFICIENCY | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.description.journalRegisteredClass | kci | - |
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