3. BIOTRANSFORMATION OF DRUGS IN THE BODY

Most drugs undergo biotransformation in the body (Fig II.7). High-hydrophilic ionized compounds are usually eliminated unchanged. The exception among lipophilic substances are inhalation anesthetic drugs, most of which are not involved in chemical reactions occurring in the body. They are eliminated via the lungs in the same form as they had been administered. Most enzymes participate in drug biotransformation, and the most important among them are microsomal enzymes of the liver (located in the endoplasmic reticulum). They metabolize foreign lipophilic compounds (of different structure), transforming them into more hyd-

Fig. II.7. Ways of drug biotransformation.

¹ Word «apparent» is used because the body can be viewed, for simplicity, as a single whole space (one-compartment model).

² In a human weighing 70 kg plasma consists of 3 l of water. Total amount of extracellular liquid is 12-15 l and total amount of water is 41 l.

rophilic. They do not have substrate specificity. Non-microsomal enzymes of various localizations (liver, intestine and other tissues, as well as plasma) are of very high significance, especially for the biotransformation of hydrophilic substances.

There are two main types of drugs bio-transformation: 1) metabolic transformation (I phase) and 2) conjugation (II phase). Metabolic transformation is a transformation occurring through oxidation, reduction and hydrolysis. For example, imipramine, ephedrine, chlorpromazine, histamine and codeine undergo oxidation. Oxidation occurs mostly due to microsomal oxidases of mixed action with participation of nicotinamide adenine dinucleotide phosphate (NADP), oxygen and P-450 cytochrome. Certain drugs undergo reduction, such as chloral hydrate, chloramphenicol, nitrazepam, etc. It occurs under the effect of nitroand azoreductases and other enzymes. Esters (procaine, atropine, acetylcholine, suxamethonium, acetylsalicylic acid) and amides (procainamide) are hydrolyzed under the impact of esterases, carboxylesterases, amidases, phosphatases, etc. There are following examples to illustrate it (Fig. II.8).