Examination of pharmacokinetics and pharmacodynamics of pyridoxamine as a protective agent of peritoneal membrane

• Project/Area Number: 25461256
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Kidney internal medicine
• Research Institution: Tokai University
• Principal Investigator: KAKUTA Takatoshi 東海大学, 医学部, 教授 (50276854)
• Co-Investigator(Kenkyū-buntansha): FUKAGAWA Masafumi 東海大学, 医学部, 教授 (00211516) ; KOBAYASHI Hiroyuki 東海大学, 医学部, 教授 (60195807)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥130,000 (Direct Cost: ¥100,000、Indirect Cost: ¥30,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
• Keywords: 腹膜透析 / 腹膜保護 / ピリドキサミン / 内服薬 / カルボニル・ストレス / carbonyl / 半減期

Outline of Final Research Achievements

Peritoneal membrane dysfunction and ultrafiltration failure are ameliorated by administration of pyridoxamine (PM), an inhibitor of carbonyl stress. The present study examined the pharmacokinetics and pharmacodynamics of PM given orally to uremic rats and to patients on peritoneal dialysis (PD). Rats were suffered subtotal nephrectomy plus 3 weeks of daily PD with daily gavage of 50 mg PM. The increase in small solute transport, mesenteric vessel densities and circulating pentosidine were mitigated in PM treated group in comparison with non-treated control. In human study, six patients undergoing PD were given a single oral dose of 600 mg PM. Pharmacokinetics was compared to that of eight healthy adults. The pharmacodynamics was assessed by the total carbonyl content in PD effluent. Total carbonyl levels decreased significantly compared with the PD effluent from the same patients without oral PM. In conclusion, PM ameliorates peritoneal carbonyl stress and thus protects the peritoneum.

Research Products

• [Journal Article] Oral administration of pyridoxamine lower peritoneal carbonyl stress in uremic rats (2016)
  • Author(s): Mori Y, Kakuta T, Miyakogawa T, Takekoshi S, Yuzawa H, Kobayashi H, Kawakami A, van Ypersele de Strihou C, Fukagawa M
  • Journal Title: Therapeutic Apheresis and Dialysis Volume: 20
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] Pyridoxamine as a Protective Agent against Progressive Deterioration of Peritoneal Function in Peritoneal Dialysis Patients (2014)
  • Author(s): Yoshitaka Miri
  • Organizer: APCN2014
  • Place of Presentation: 品川プリンスホテル