Excretion and reabsorption of drugs

Previously in this chapter, the pH partition hypothesis was applied to the absorption of drugs across biological membranes following administration by the oral route. The same types of physicochemical processes occur when drugs are reabsorbed into the bloodstream following excretion by the kidneys. 

The kidneys receive a large blood flow (approximately a quarter of the total cardiac output of 5 litres per minute) and from this volume of blood approximately 170 litres of filtrate are produced every day Clearly, the body would quickly become dehydrated if this volume of fluid were lost to the sewage system, so most of it is reabsorbed from the kidney tubule and returned to the bloodstream. Small molecules that are dissolved in the glomerular filtrate are also reabsorbed back into the bloodstream, either by passive diffusion (which obeys Fick s law) or by the utilisation of energy in an active transport process similar to the mechanisms for gut absorption discussed previously. It should be realised that reabsorption from the glomerular filtrate and return to the bloodstream are involved in the duration of action of many drugs, and a drug molecule may be filtered and reabsorbed many times before it is finally excreted from the body. 

In cases of drug overdose it is desirable to eliminate the toxic drug from the body as quickly as possible and techniques have been devised to 

If the drug taken in overdose is a base, for example, a benzodiazepine tranquilliser or an antihistamine, excretion should be favoured by acidification of the urine. Agents that may be used to achieve this include ammonium chloride, NH Cl- (an acidic salt by partial hydrolysis) and ascorbic acid (vitamin C). If the pH of the urine is artificially lowered, the technique is called forced acid diuresis. 

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Important mechanisms involved in the renal excretion and reabsorption of drugs have been reviewed by Reidenberg (15) and are shown in Table 5.1. 

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