Alteration of renal drug transporters during growth and its effects on the pharmacokinetics

• Project/Area Number: 23790182
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Kyoto Pharmaceutical University
• Principal Investigator: MOTOHASHI Hideyuki 京都薬科大学, 講師 (30359822)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 薬学 / 医療系薬学 / トランスポータ / 腎臓 / 薬物腎排泄 / 小児 / 薬物動態

Research Abstract

The purpose of this study was to elucidate the developmental changes in the expression of transporters and their effects on the renal excretion of drugs. The protein expression of the transporters were very low at postnatal day 0 and gradually increased with age. On the other hand, the tubular secretion of PSP was significantly lower in postnatal day 14 rats than adult rats. These results indicate that age-dependent changes in organic anion transporter expression affect the tubular secretion of anionic drugs in pediatric patients.

Research Products

• [Journal Article] Precise comparison of protein localization among OCT, OAT, and MATE in human kidney. (2013)
  • Author(s): Motohashi H, Nakao Y, Masuda S, Katsura T, Kamba T, Ogawa O, Inui K.
  • Journal Title: J Pharm Sci. Volume: Vol. 102
  • Peer Reviewed
• [Journal Article] Multidrug and toxin extrusion family SLC47: Physiological, pharmacokinetic and toxicokinetic importance of MATE1 and MATE2-K. (2013)
  • Author(s): Motohashi H, Inui K.
  • Journal Title: Mol Aspects Med. Volume: Vol. 34 Pages: 661-668
  • Peer Reviewed
• [Journal Article] Organic Cation Transporter OCTs (SLC22) and MATEs (SLC47) in the Human Kidney. (2013)
  • Author(s): Motohashi H, Inui K.
  • Journal Title: AAPS J. Volume: Vol.15 Pages: 581-588
  • Peer Reviewed
• [Journal Article] Precise comparison of protein localization among OCT, OAT, and MATE in human kidney. (2013)
  • Author(s): Motohashi H, Nakao Y, Masuda S, Katsura T, Kamba T, Ogawa O, Inui K.
  • Journal Title: Journal of Pharmaceutical Sciences Volume: 102 Issue: 9 Pages: 3302-3308
  • DOI: 10.1002/jps.23567
  • Peer Reviewed
• [Journal Article] Multidrug and toxin extrusion family SLC47: Physiological, pharmacokinetic and toxicokinetic importance of MATE1 and MATE2-K. (2013)
  • Author(s): Motohashi H
  • Journal Title: Mol Aspects Med Volume: 34 Issue: 2-3 Pages: 661-668
  • DOI: 10.1016/j.mam.2012.11.004
  • Peer Reviewed
• [Journal Article] Organic Cation Transporter OCTs (SLC22) and MATEs (SLC47) in the Human Kidney. (2013)
  • Author(s): Motohashi H
  • Journal Title: AAPS J Volume: 15 Issue: 2 Pages: 581-588
  • DOI: 10.1208/s12248-013-9465-7
  • Peer Reviewed
• [Journal Article] Developmental expression of renal organic anion transporters in rat kidney and its effect on renal secretion of phenolsulfonphthalein. (2012)
  • Author(s): Nomura M, Motohashi H, Sekine H, Katsura T, Inui K.
  • Journal Title: Am J Physiol Renal Physiol. Volume: Vol. 302 Pages: 1640-1649
  • Peer Reviewed
• [Journal Article] Developmental expression of renal organic anion transporters in rat kidney and its effect on renal secretion of phenolsulfonphthalein (2012)
  • Author(s): Maki Nomura
  • Journal Title: American Journal of Physiology - Renal Physiology Volume: 302 Issue: 12 Pages: F1640-F1649
  • DOI: 10.1152/ajprenal.00525.2011
  • Peer Reviewed
• [Journal Article] Developmental expression of renal organic anion transporters in rat kidney and its effect on renal secretion of phenolsulfonphthalein (2012)
  • Author(s): Nomura M, Motohashi H, Sekine H, Katsura T, Inui K
  • Journal Title: Am J Physiol Renal Physiol Volume: in press
  • Peer Reviewed
• [Journal Article] Effects of metabolic acidosis on expression levels of renal drug transporters. (2011)
  • Author(s): Gaowa A, Motohashi H, Katsura T, Inui K.
  • Journal Title: Pharm Res. Volume: Vol.28 Pages: 13-18
  • Peer Reviewed
• [Journal Article] Effects of metabolic acidosis on expression levels of renal drug transporters (2011)
  • Author(s): Gaowa A, et al
  • Journal Title: Pharmaceutical Research Volume: 28 Issue: 5 Pages: 1023-1030
  • DOI: 10.1007/s11095-010-0348-7
  • Peer Reviewed
• [Presentation] バラシクロビル投与時における腎機能障害の発症と患者背景に関する解析 (2013)
  • Author(s): 北野あすか
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] カフェイン大量補助化学療法における体内動態シミュレーションと個別投与設計の可能性 (2013)
  • Author(s): 池野有美
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] バラシクロビル投与時における 腎機能障害の発症と患者背景に関する解析 (2013)
  • Author(s): 北野あすか
  • Organizer: 日本薬学会第133年会
  • Place of Presentation: パシフィコ横浜
• [Presentation] 文献調査にもとづいたゲフィチニブ耐性非小細胞肺がんにおける化学療法の比較 (2012)
  • Author(s): 酒井美和
  • Organizer: 日本薬学会近畿支部総会・大会
  • Place of Presentation: 武庫川女子大学
• [Presentation] 蛍光測定を利用した手指衛生評価法とパームチェック法との比較 (2012)
  • Author(s): 岡本圭史
  • Organizer: 日本薬学会近畿支部総会・大会
  • Place of Presentation: 武庫川女子大学
• [Presentation] 精神疾患と自殺に関わる社会的要因に関する研究-都道府県別解析による精神疾患の現状把握- (2012)
  • Author(s): 藤本敦子
  • Organizer: 日本薬学会近畿支部総会・大会
  • Place of Presentation: 武庫川女子大学
• [Presentation] メトロニダゾール軟膏基剤のin vitro吸水試験方法に関する検討 (2012)
  • Author(s): 中川静子
  • Organizer: 日本薬学会近畿支部総会・大会
  • Place of Presentation: 武庫川女子大学
• [Presentation] 精神疾患と自殺に関わる社会的要因に関する研究－都道府県別解析による精神疾患の現状把握－ (2012)
  • Author(s): 藤本敦子
  • Organizer: 日本薬学会近畿支部総会・大会
  • Place of Presentation: 武庫川女子大学
• [Presentation] メトロニダゾール軟膏基剤の in vitro 吸水試験方法に関する検討 (2012)
  • Author(s): 中川静子
  • Organizer: 日本薬学会近畿支部総会・大会
  • Place of Presentation: 武庫川女子大学
• [Presentation] Developmental expression of renal organic anion transporters and its effect on the renal drug secretion (2011)
  • Author(s): Nomura M
  • Organizer: 第26回日本薬物動態学会年会
  • Place of Presentation: 広島国際会議場
  • Year and Date: 2011-11-18
• [Presentation] Effect of Metabolic Acidosis on Urinary Drug Excretion (2011)
  • Author(s): Gaowa A
  • Organizer: 4th Asia Pacific Regional Meeting of ISSX
  • Place of Presentation: TAINAN, Taiwan
• [Presentation] アシドーシス時における腎薬物トランスポータの機能及び発現変動 (2011)
  • Author(s): 阿栄高娃
  • Organizer: 日本薬剤学会第26年会
  • Place of Presentation: タワーホール船堀
• [Presentation] Developmental expression of renal organic anion transporters and its effect on the renal drug secretion (2011)
  • Author(s): Nomura M, Motohashi H, Sekine H, Katsura T
  • Organizer: 第２６回日本薬物動態学会年会
  • Place of Presentation: 広島国際会議場
• [Presentation] Effect of Metabolic Acidosis on Urinary Drug Excretion (2011)
  • Author(s): Gaowa A, Motohashi H, Katsura T, Inui K
  • Organizer: 4th Asia Pacific Regional Meeting of ISSX
  • Place of Presentation: TAINAN
• [Book] Annual Review腎臓2013Clinical nephrology尿細管・間質障害副作用発現における腎薬物トランスポータの寄与 (2013)
  • Author(s): 本橋秀之
  • Total Pages: 7
  • Publisher: 中外医学社
• [Book] Annual Review腎臓2013 Clinical nephrology 尿細管・間質障害 副作用発現における腎薬物トランスポータの寄与 (2013)
  • Author(s): 本橋秀之
  • Total Pages: 7
  • Publisher: 中外医学社