Sakurai Yuji, Motohashi Hideyuki, Ueo Harumasa, Masuda Satohiro, Saito Hideyuki, Okuda Masahiro, Mori Noriko, Matsuura Motokazu, Doi Toshio, Fukatsu Atsushi, Ogawa Osamu, Inui Ken-ichi
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Pharm Res. 2004 Jan;21(1):61-7. doi: 10.1023/b:pham.0000012153.71993.cb.
Because the urinary excretion of drugs is often decreased in renal diseases, dosage regimens are adjusted to avoid adverse drug reactions. The aim of present study was to clarify the alteration in the levels of renal drug transporters and their correlation with the urinary drug excretion in renal diseases patients.
We quantified the mRNA levels of human organic anion transporters (hOATs) by real-time polymerase chain reaction and examined the excretion of the anionic drug, cefazolin, in renal disease patients. Moreover, transport of cefazolin by hOAT1 and hOAT3 were examined using HEK293 transfectants.
Among four hOATs, the level of hOAT1 mRNA was significantly lower in the kidney of patients with renal diseases than in the normal controls. The elimination constant of cefazolin showed a significant correlation with the values of phenolsulfonphthalein test and mRNA levels of hOAT3. The uptake study using HEK293 transfectants revealed that cefazolin and phenolsulfonphthalein were transported by hOAT3.
These results suggest that hOAT3 plays an important role for anionic drug secretion in patients with renal diseases and that the expression levels of drug transporters may be related to the alteration of renal drug secretion.
由于肾脏疾病常导致药物经尿液排泄减少，因此需调整给药方案以避免药物不良反应。本研究旨在阐明肾脏疾病患者肾药物转运体水平的变化及其与尿药物排泄的相关性。
我们通过实时聚合酶链反应定量检测人有机阴离子转运体（hOATs）的mRNA水平，并检测肾脏疾病患者中阴离子药物头孢唑林的排泄情况。此外，使用HEK293转染细胞研究hOAT1和hOAT3对头孢唑林的转运情况。
在四种hOATs中，肾脏疾病患者肾脏中hOAT1 mRNA水平显著低于正常对照组。头孢唑林的消除常数与酚磺酞试验值及hOAT3的mRNA水平显著相关。使用HEK293转染细胞的摄取研究表明，头孢唑林和酚磺酞可被hOAT3转运。
这些结果表明，hOAT3在肾脏疾病患者阴离子药物分泌中起重要作用，且药物转运体的表达水平可能与肾脏药物分泌的改变有关。
