Thought about drug discovery – pharmacology vs toxicology.

I have been taking a number of drug discovery related courses lately and coupled with own lab experience working with anti-cancer platinum drugs, here’s a little reflection on the process of drug discovery. Drug discovery is a long process and it involves numerous parties with different interests – scientists, big pharmaceutical firms, clinical practitioners and the FDA.

Scientists are predominantly concerned about pharmacological effect as well as some degree of novelty. They are interested in making drugs that are better than existing drugs in the market be it in terms of pharmacokinetics (what the body does to the drug) or pharmacodynamics (what the drug does to the body) of the drug. They also like to make drugs that are able to achieve some kind of novel therapeutic synergistic function. They usually use a Hit-To-Lead approach by synthesizing a library of drug compounds and evaluating their properties in vitro to find a lead compound. The lead compound(s) will then be tested in preclinical studies on mice and if successful, the drug can be patented and sent for clinical trials in the hospitals. Clinical trials are important mainly to determine the safety profile of the drug and to test if the drug is able to achieve its promised pharmacological effect. If successful, the drug can then be approved by authorities like the FDA in the US.

We learnt that because the number of subjects tested during clinical trials is few as compared to the number of people who eventually take the drug, hence the subjects used for clinical trials are not representative of the profile of all the targeted patients. Often a small population of patients develop adverse reactions to the drugs – toxic effects of the drug that no one is aware of during the earlier stages of testing. What happens after is that researchers try to understand how this drug can possibly be metabolized to result in such toxic effects. Many a times, drugs are subsequently withdrawn from the market because of the toxic effects that they caused to a small population of patients.

This is a really sad ending for the drug because a lot of time and effort has been wasted at making and testing the drug. I wonder if something can be changed to make the process less wasteful and more productive. From the utilitarian perspective, I wonder how justifiable it is to withdraw a pharmacologically superior drug because of the adverse toxic effects it has on a small population of people. Is it possible to “screen” patients for certain biomarkers prior to the administration of the drug to evaluate their suitability for taking the drug? I remember when I had vaccines, the doctor made adverse side reactions sound as though it’s a matter of chance. But I think it’s possible to eludicate the metabolic pathway resulting in toxic effects…Then toxicology of the drug can ideally become something important to keep in mind instead of something worthy to cause the drug to be withdrawn from the market. Is this area then significant enough for scientists to explore as part of their research interests?

I also wonder if it is possible to motivate researchers to design drugs that are less toxic even though doing so may compromise the pharmacological properties and novelty. I feel that the academia is plagued with too many compounds with novel chemistry but are unlikely to be developed into real clinical drugs. Priorities and significance must be changed.

Leave a Reply

Fill in your details below or click an icon to log in: Logo

You are commenting using your account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s