Drug distribution and survival

In Chapter 7, we concentrated on the interaction of drugs with binding sites. However, the compound which has the best binding interaction with its receptor is not necessarily the best drug to use in medicine. There are other variables which have to be taken into account. 

The drug has to be stable enough to survive a rather tortuous journey through the body s circulatory system. It also has to be capable of negotiating barriers put in its way and not be diverted from its target. 

For example, consider a drug taken as a pill. It has to dissolve in aqueous solution. It has to survive the acid of the stomach, then be absorbed from the gastrointestinal tract into the bloodstream. To do that it has to negotiate barriers in the form of cell membranes. It has to survive the destructive tendencies of the liver and its enzymes. It has to survive the enzymes present in the blood. If it is a lipophilic drug, it may be taken up by fat tissue. If it is anionic, it may get bound by plasma protein and if it is cationic, it may be bound by nucleic acids. It has to avoid being excreted by the kidneys or the bile duct. If the drug is aimed at the brain, it has to cross another cell barrier known as the blood-brain barrier. If it is to react with an enzyme, it has to negotiate another cell membrane to reach that. 

Only then will the drug interact with its receptor or enzyme. As far as the drug is concerned, it is a long, strenuous, and dangerous journey. 

Many of these problems can be avoided by giving the drug as an intravenous or intramuscular injection, but clearly orally administered drugs are preferred by the patient and if at all possible, drug design aims at an orally active compound. Let us look again at the journey which has to be followed by an orally administered drug. 

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