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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 한국약제학회 Journal of Pharmaceutical Investigation Journal of Pharmaceutical Investigation Vol.54 No.3
- 발행연도
- 2024.5
- 수록면
- 389 - 402 (14page)
- DOI
- 10.1007/s40005-023-00659-2
이용수
초록· 키워드
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Purpose This study investigated effects of 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] 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)2D3 (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)2D3-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)2D3. 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)2D3 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.
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