that produce an adverse effect on the fetus. Toxicity problems have resulted in
many drugs being withdrawn from the market, as shown in table 3.3. As shown in
figure 3.11, toxicity problems are a major cause of drug rejection during the development process.
Successful completion of the four phases of human clinical trials enables a drug to
be widely distributed for the treatment of human disease. However, a simple reality of
drug discovery is that drugs are developed by industry. The lead compound may have
been identified in an academic university-based laboratory, but the clinical trials are
invariably completed by the industrial sector. Academic institutions, governments, or
international organizations (e.g., the World Health Organization, WHO) do not develop
drugs. Because of this, drug molecules tend to be developed only if they have a good
prospect for being profitable. In order to be profitable, a drug molecule should be
patented so that the vendor can enjoy exclusive rights to its marketing. Although a
discussion of the criteria for patentability is beyond the scope of this book, the drug
162
MEDICINAL CHEMISTRY
Table 3.3 Approved Drugs Withdrawn Because of Toxicity
Drug
Year
Adverse reaction
Astemizole
1998
Interactions (e.g., with grapefruit juice)
Benoxaprofen
1982
Liver damage
Centoxin
1993
Increased mortality
Cerivastatin
2001
Muscle breakdown
Cisapride
2000
Cardiac arrhythmias
Clioquinol
1975
Optic neuropathy (eye problem)
Dexfenfluramine
1997
Cardiac valve abnormalities
Fenfluamine
1997
Cardiac valve abnormalities
Flosequinan
1993
Increased mortality
Indoprofen
1984
Gastrointestinal bleeding/perforation
Metipranolol 0.6% eyedrops
1990
Anterior uveitis (eye problem)
Mibefradil
1998
Many drug interactions
Nomifensine
1986
Hemolytic anemia
Noscapine
1991
Gene toxicity
Remoxipride
1994
Aplastic anemia
Sertindole
1998
Cardiac arrhythmias
Suprofen
1987
Renal impairment
Temafloxacin
1992
Various serious adverse effects
Terodiline
1991
Cardiac arrhythmias
Tolcapone
1998
Hepatobiliary disorders
Triazolam
1991
Psychiatric disorders
Troglitazone
1997
Hepatic disorders
Zimeldine
1983
Hypersensitivity
Zomepirac
1983
Anaphylaxis
many drugs being withdrawn from the market, as shown in table 3.3. As shown in
figure 3.11, toxicity problems are a major cause of drug rejection during the development process.
Successful completion of the four phases of human clinical trials enables a drug to
be widely distributed for the treatment of human disease. However, a simple reality of
drug discovery is that drugs are developed by industry. The lead compound may have
been identified in an academic university-based laboratory, but the clinical trials are
invariably completed by the industrial sector. Academic institutions, governments, or
international organizations (e.g., the World Health Organization, WHO) do not develop
drugs. Because of this, drug molecules tend to be developed only if they have a good
prospect for being profitable. In order to be profitable, a drug molecule should be
patented so that the vendor can enjoy exclusive rights to its marketing. Although a
discussion of the criteria for patentability is beyond the scope of this book, the drug
162
MEDICINAL CHEMISTRY
Table 3.3 Approved Drugs Withdrawn Because of Toxicity
Drug
Year
Adverse reaction
Astemizole
1998
Interactions (e.g., with grapefruit juice)
Benoxaprofen
1982
Liver damage
Centoxin
1993
Increased mortality
Cerivastatin
2001
Muscle breakdown
Cisapride
2000
Cardiac arrhythmias
Clioquinol
1975
Optic neuropathy (eye problem)
Dexfenfluramine
1997
Cardiac valve abnormalities
Fenfluamine
1997
Cardiac valve abnormalities
Flosequinan
1993
Increased mortality
Indoprofen
1984
Gastrointestinal bleeding/perforation
Metipranolol 0.6% eyedrops
1990
Anterior uveitis (eye problem)
Mibefradil
1998
Many drug interactions
Nomifensine
1986
Hemolytic anemia
Noscapine
1991
Gene toxicity
Remoxipride
1994
Aplastic anemia
Sertindole
1998
Cardiac arrhythmias
Suprofen
1987
Renal impairment
Temafloxacin
1992
Various serious adverse effects
Terodiline
1991
Cardiac arrhythmias
Tolcapone
1998
Hepatobiliary disorders
Triazolam
1991
Psychiatric disorders
Troglitazone
1997
Hepatic disorders
Zimeldine
1983
Hypersensitivity
Zomepirac
1983
Anaphylaxis