1. Bourdi, Mohammed. Ph.D.
Dr. Mohammed Bourdi is a staff scientist at NIH. In
September 1992, he received his Ph.D. in Biochemistry
and Pharmacochemistry, from Renes Descartes
University, Paris, France. From 1993 to 1998, he was a
postdoctoral fellow at the Molecular and Cellular
Toxicology Section (Laboratory of Molecular
Immunology), NIH, Bethesda, Maryland. He became a
research fellow from 1998 to 2001. Since 2001 he has
been a staff scientist in the some laboratory.
His primary research interest is the study of the
molecular and cellular basis of drug-induced liver
disease, particularly those that have an immune basis.
6. Reasons why drugs are withdrawn from the market
Torsadede
Pointes 33%
Cardiovascular
12%
Hepatotoxicity
32%
Haematology-
BM9%
Other 8%
Nervous System
2%
Immunotox2%
GI 2%
Drug Discov Today 14, 162-167,2009
Hepatotoxicity
32%
7.
8. Many factors may influence iDILI* risk
Environment
Genetics
Age
Dose
Compliance
Diet
Disease
Other
Meds
Image from Ramachandran R and Kakar, (2009) J Clin Pathol 62:481-492
* Idiosycratic Drug-Induced Liver Injury.
9.
10. Courtesy John Senior
Acute Idiosyncratic Hepatotocellular Injury (AIHI)
Time Course of Liver Tests
Patient #1234, caucasian male 80, Drug X
0.1
1.0
10.0
100.0
-30
0
30
60
90
120
150
180
Study Day
LiverTestValues,xULRR
ALTx
TBLx
ASTx
ALPx
hosp
diedstart stop
probably
drug-induced
CourtesyJohnSenior
Typical Acute Idiosyncratic Hepatocellular Injury
*
**
11. Top 10 drugs with fatal liver injury reported to the WHO
Collaborating Center for International Drug Monitoring
Bjornsson & Olsson DLD, 2005
