4. ROUTES OF DRUG ELIMINATION FROM THE BODY

Drugs, their metabolites and conjugates are mainly eliminated with urine and bile.

In the kidneys low-molecular compounds, dissolved in plasma (not bound to proteins), are filtered through membranes of glomerular capillaries and glomerular capsules (Fig. II.11 and II.12). Besides, active secretion of substances in proximal tubules with the participation of the transport systems is essential. This is the elimination route of organic acids and bases, penicillins, salicylates, sulfonamides, quinine, histamine, thiazides, etc. Some lipophilic compounds can penetrate from blood into tubular lumen (proximal and distal) by simple diffusion through their walls.

The elimination of substances greatly depends on their reabsorption in renal tubules. Drugs are reabsorbed mainly by simple diffusion. This mainly concerns lipophilic non-polar compounds, easily penetrating through biologic membranes. Polar compounds are poorly reabsorbed from the renal tubules. That is why elimination of weak acids and bases greatly depends on urine pH. Thus, when urine pH is alkaline, there is an increase in the elimination of acidic compounds (for example, salicylic acid, phenobarbital). When urine pH is

Fig. II.11. Basic processes affecting renal excretion of pharmacological substances.

Fig. II.12. Principles of renal excretion.

acidic, elimination ofbases increases (imipramine, etc.). The reason for this is the ionization of the mentioned compounds which prevents their reabsorption from the renal tubules.

Active transport is involved in reabsorption of a number of endogenous substances (amino acids, glucose, uric acid).

Significant mechanisms of the elimination of a number of drugs (tetracyclines, penicillins, phenytoin, colchicine, other) and especially products of their transformation is their transfer with bile into the intestine. A certain proportion of the drug is then eliminated with faeces, and the rest is reabsorbed. The cycle continues on, with the compound then again being eliminated into the intestine and so on (so-called hepato-intestinal circulation or hepatic recirculation; Fig. II.13).