Study on interspecies-difference in tissue distribution of weakly basic drugs and prediction of the distribution in human

• Project/Area Number: 04454533
• Research Category: Grant-in-Aid for General Scientific Research (B)
• Allocation Type: Single-year Grants
• Research Field: Biological pharmacy
• Research Institution: HIROSHIMA UNIVERSITY
• Principal Investigator: YATA Noboru Hiroshima University School of Medicine, Professor, 医学部, 教授 (70028835)
• Co-Investigator(Kenkyū-buntansha): MURAKAMI Teruo Hiroshima University School of Medicine, Associate Professor, 医学部, 助教授 (20136055) ; HIGASHI Yutaka Hiroshima University School of Medicine, Associate Professor, 医学部, 助教授 (90127697)
• Project Period (FY): 1992 – 1994
• Project Status: Completed (Fiscal Year 1994)
• Budget Amount: ¥3,400,000 (Direct Cost: ¥3,400,000); Fiscal Year 1994: ¥200,000 (Direct Cost: ¥200,000); Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000); Fiscal Year 1992: ¥2,500,000 (Direct Cost: ¥2,500,000)
• Keywords: Tissue distribution / Quinidine / Weakly basic drugs / Phosphatidylserine / Rats / Mice / Rabbits / Guinea-pigs / フォスファチジルセリン / 塩基性薬物 / ホスファチジルセリン含量 / 種差 / 相互作用 / アニマルスケールアップ / ヒトでの分布予測

Research Abstract

The role of phosphatidylserine (PhS) in the tissue distribution of quinidine (Kp value) was investigated in CCI_4-intoxicated rats, turpentine-treated rats, normal rabbits, normal mice and normal guinea-pigs.
In all animal models, a linear relationship between the Kp value of unbound quinidine in plasma and tissue PhS concentration in various tissues was observed.
Also, the obtained Kp values were almost comparable among different animals examined.
These results indicate that PhS is a determinant in tissue distribution of quinidine in experimental animals, and no interspecies-difference was observed.
Above finding may indicate that the Kp value of weakly basic drugs in human is also predictable from the relationship between the Kp value of unbound drug concentration in plasma and tissue PhS concentration in experimental animals.

Research Products

• [Publications] N.Sugihara,: "The influence of increased plasma protein binding on the disposition of quinidine in turpentine-treated rats" Biological & Pharmaceutical Bulletin. 16. 63-67 (1993)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] N.Sugihara, K.Furuno, N.Kita, T.Murakami, N.Yata: "The influence of increased plasma protein binding on the disposition of quinidine in turpentine-treated rats" Biol. Pharm. Bull.16、. 63-67 (1993)
  • Description: 「研究成果報告書概要(欧文)」より
• [Publications] Akio Nishiura: "A possible contribution of Phospholipids in tissue distribution of quinidine in rats" Journal of Pharmacobio-Dynamics. 9. 819-828 (1986)
• [Publications] Akio Nishiura: "Role of acidic phospholipids in tissue distribution of quinidine in rats" Journal of Pharmacobio-Dynamics. 10. 135-141 (1987)
• [Publications] Akio Nishiura: "Role of Phosphatidylserine in the lung cellular and subcellular distribution of quinidine in rats" Pharmaceutical Research. 5. 209-213 (1988)
• [Publications] Noboru Yata: "Phosphatidylserine as a determinant for the tissue distribution of weakly basic drugs in rats" Pharmaceutical Research. 7. 1019-1025 (1990)