WordNet

PrepTutorEJDIC

Strategic proposals for avoiding toxic interactions with drugs for clinical use during development and after marketing of a new drug--proposals for designing non-clinical and clinical studies--is the non-clinical study useful?

Ozawa N.SourceUpjohn Pharmaceuticals Limited, Tsukuba Research Laboratories, Ibaraki, Japan.
The Journal of toxicological sciences.J Toxicol Sci.1996 Dec;21(5):323-9.
Since sorivudine incident has happened in Japan in 1993, an adverse drug-drug interaction has been of special meanings at each step of new drug development including the discovery step, NDA process, and on market. While it is known that several mechanisms are involved in the drug-drug interactions,
PMID 9035045

"S2-5-1) STRATEGIC PROPOSALS FOR AVOIDING TOXIC INTERACTIONS WITH DRUGS FOR CLINICAL USE DURING DEVELOPMENT AND AFTER MARKETING OF A NEW DRUG : PROPOSALS FOR DESIGNING NON-CLINICAL AND CLINICAL STUDIES : IS THE NON-CLINICAL STUDY USEFUL? (<SYMPOSIUM 2>Strategy how we can learn drug-drug interaction during the development of a new drug)

OZAWA Naoki
Journal of toxicological sciences 21(5), 323-329, 1996-12-20
… Since sorivudine incident has happened in Japan in 1993, an adverse drug-drug interaction has been of special meanings at each step of new drug development including the discovery step, NDA process, and on market. …
NAID 110001805869

参考1

1993年に日本で起こった薬害。
抗ウイルス薬の新薬として市販されたソリブジン(sorivudine, 1-b-D-arabinofuranosyl-(E)-5-(2-bromovinyl)uracilは水痘・帯状疱疹ウイルスに対する抗ウイルス作用が高く、帯状疱疹の治療薬として期待されていた。
5-フルオロウラシル(5-FU)との併用により副反応が出現し、死亡を出すに至った。
副作用の発現機序は、ソリブジンの代謝産物であるBVUにより5-FUの代謝がブロックされ、血中5-FU濃度が致死量を上回ることによる。

1. [free PDF][Molecular toxicological mechanism of the lethal interactions of the new antiviral drug, sorivudine, with 5-fluorouracil prodrugs and genetic deficiency of dihydropyrimidine dehydrogenase].

Watabe T, Ogura K, Nishiyama T.SourceDepartment of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji City, Tokyo 192-0392, Japan. watabet@ps.toyaku.ac.jp
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan.Yakugaku Zasshi.2002 Aug;122(8):527-35.
In 1993, there were 18 acute deaths in Japanese patients who had the viral disease herpes zoster and were treated with the new antiviral drug sorivudine (SRV, 1-beta-D-arabinofuranosyl-(E)-5-(2-bromovinyl)uracil). All the dead patients had received a 5-fluorouracil (5-FU) prodrug as anticancer chemo
PMID 12187768

2. [free PDF]Lethal drug interactions of sorivudine, a new antiviral drug, with oral 5-fluorouracil prodrugs.

Okuda H, Nishiyama T, Ogura K, Nagayama S, Ikeda K, Yamaguchi S, Nakamura Y, Kawaguchi Y, Watabe T.SourceDepartment of Drug Metabolism and Molecular Toxicology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
Drug metabolism and disposition: the biological fate of chemicals.Drug Metab Dispos.1997 May;25(5):270-3.
Rats were orally co-administered sorivudine (SRV: 1-beta-D-arabinofuranosyl-(E)-5-(2-bromovinyl)uracil), a new oral antiviral drug for herpes zoster, with the oral anticancer drug tegafur (FT: 1-(2-tetrahydrofuryl)-5-fluorouracil as a prodrug of 5-fluorouracil (5-FU) once daily to investigate a toxi
PMID 9152608