Biotransformation and Metabolism of Drugs

Created on Mon, 06/29/2015 - 22:13
Last updated on Thu, 11/16/2017 - 17:08

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This chapter answers parts from Section B(iv) of the 2017 CICM Primary Syllabus, which expects the exam candidate to "describe the mechanisms of drug clearance and metabolism". Biotransformation is a handy term which describes the latter; it is defined by Wikipedia as "the chemical modification (or modifications) made by an organism on a chemical compound".  As such, the term is generally used to refer to hepatic metabolism of drugs, but could in fact apply to various other settings.

This brief revision summary is included here to indulge the authors' own demented need for completeness. In actual fact the college past papers have never included any reference to biotransformation in its broadest definition, and only one mention of hepatic clearance processes (in Question 20 from the first paper of 2016). Free from the need to answer any actual exam-oriented learning objectives, this chapter is therefore a largely pointless vanity exercise, and the time-poor exam candidate can skip it in favour of more examinable topics.

If for whatever reason one is compelled to not only read on, but also to read more widely, one would be hard pressed to find a better resource than this (somehow freely available) Chapter 6, "Biotransformation of xenobiotics" from Casarett and Doulls Toxicology: The Basic Science of Poisons. 

Definition of biotransformation 

The official college doctrine (Birkett, 2009) has no such definition (in fact a search for "biotransformation" in the entire text yields zero results) and so a person in search of guidance turns to Google. The Pharmacology and Experimental Therapeutics Department Glossary at Boston University School of Medicine offers the following definition:

"Chemical alteration of an agent (drug) that occurs by virtue of the sojourn of the agent in a biological system".

Note how the chemical must merely soujourn in a biological system; no mention is made of what the system must consist of. This opens the definition to include pharmacologically important chemical reactions. The abovelinked glossary goes on to expand the definition using examples. For instance, if a radioisotope decays within the body, even though a chemical alteration results, it is not considered biotransformation (because it does not occur by virtue of the sojourn, i.e. that decay would have happened no matter where the isotope was). Similarly, a puddle of in vitro cultured cells or even a purified enzyme solution may act on a chemical, and that would be called biotransformation because a biological system was involved, even if it were totally separated form any actual living organism. In this manner, biotransformation is a term which can be applied

Drug biotransformation versus drug metabolism

Why don't we just call it "drug metabolism"? The drugs get metabolised, don't they? Indeed the terminology is pervasive. Products of drug biotransformation are called metabolites; people whose inherited enzyme deficiency results in slowed hepatic drug clearance are called poor metabolisers and so on. The terms seem so interchangeable that one occasionally finds both used in the space of the same article title. Is this a legitimate use of the term, and if so, then why do we have two words to describe the same thing?

Well. It actually seems reasonable to use the terms synonymously, even though the term "metabolism" should really be reserved for nutritive processes. Serious sources keep using both terms interchangeably (eg. Rowlands' Clinical Pharmacokinetics, Jambhekar's Basic Pharmacokinetics, and the mystical grimoire of Goodman and Gilman).

In order to make sense of these matters, the author may take unusual liberties by offering an original synthesis. In general, the sources seem to use the term "biotransformation" to describe the metabolic processes which chemically alter the drugs after they have been administered to an organism. In short, "metabolism of drugs" is a form of biotransformation which happens to drugs in a body, whereas "biotransformation" is a more general term which applies equally well to the actions of a disembodied enzyme digesting an oil slick. 



Parkinson, Andrew, and Brian W. Ogilvie. "Chapter 6: Biotransformation of xenobiotics." In:  "Casarett and Doulls Toxicology: The Basic Science of Poisons" 6th ed.  (2001).

Hollunger, Gunnar. "On the Metabolism of Lidocaine II. The Biotransformation of Lidocaine." Basic & Clinical Pharmacology & Toxicology 17.4 (1961): 365-373.