Human Drug Metabolism

Introduction It has been said that if a drug has no side effects, then it is unlikely to work. Drug therapy labours under the fundamental problem that usually every single cell in the body has to be treated just to exert a beneficial effect on a small group of cells, perhaps in one tissue. Although […]

Consequences of drug concentration changes (Introduction) (Human Drug Metabolism)

If there are large changes in the rate of removal of a drug, then this can lead in extremis to severe problems in the outcome of the patient’s treatment: the first is drug failure, whilst the second is drug toxicity (Figure 1.2). These extremes and indeed all drug effects are directly related to the blood […]

Clearance (Introduction) (Human Drug Metabolism)

Definitions The consequences for the patient when drug concentrations either fall below the therapeutic window or exceed it can be life threatening. The rate of removal of the drug from the body determines whether it will disappear from, or accumulate in the patient’s blood. A concept has been devised to understand and measure rate of […]

Hepatic extraction and intrinsic clearance (Introduction) (Human Drug Metabolism)

High extraction drugs Hepatic extraction is a useful term to measure how easily the liver can process, or metabolize, a given drug or toxin. The term ‘hepatic extraction’ effectively means the difference between the drug level in blood that enters the liver (100 per cent) and the amount that escapes intact and unmetabolized (that is, […]

First pass and plasma drug levels (Introduction) (Human Drug Metabolism)

Clearance is the removal of drug from all tissues and usually the liver is seen as the major force in the clearance of drugs. However, this is an oversimplification, as other tissues can clear drugs and in the real world of a drug entering the body, the gut makes a significant contribution to clearance (Figure […]

Drug and xenobiotic metabolism (Introduction) (Human Drug Metabolism)

From the therapeutic point of view, it is essential to ensure that drug concentrations remain within the therapeutic window and neither drug failure, nor drug toxicity, occur in the patient. To understand some of the factors related to drug metabolism that can influence the achievement of these aims. •    What are the metabolic or biotransformational […]

Biotransforming enzymes (Drug Biotransformational Systems – Origins and Aims) (Human Drug Metabolism)

John Lennon once said ‘Before Elvis, there was nothing’. Biologically, this could be paraphrased along the lines of ‘Before bacteria, there was nothing’. Bacterial life has existed on this planet for more than 3.5 billion years and it first emerged in a far more hostile environment than that of today. Bacteria would have had to […]

Threat of lipophilic hydrocarbons (Drug Biotransformational Systems – Origins and Aims (Human Drug Metabolism)

Organisms such as oysters that cannot rid themselves of lipophilic aromatic and nonaromatic hydrocarbons tend to accumulate these chemicals to toxic levels. Mudskippers, however, are less vulnerable to such toxicity as they use their biotransforming enzymes to remove these chemicals from their systems. With the advent of human dependence on petrochemical technology, vast amounts of […]

Cell communication (Drug Biotransformational Systems – Origins and Aims) (Human Drug Metabolism)

Signal molecule design At some point in evolution, single-cell life forms began to coalesce into multi-cell organizations, allowing advantages in influencing and controlling the cells’ immediate environment. Further down this line of development, groups of cells differentiated to perform specialized functions, which other cells would not then need to carry out. At some point in […]

Potential food toxins (Drug Biotransformational Systems – Origins and Aims) (Human Drug Metabolism)

As living organisms developed in complexity and their diets expanded to include many types of plants and animals, it was clearly necessary to evolve a system that would protect an organism from food toxins. This process was probably greatly accelerated by the evolution of land animals from their sea-going ancestors. Diets rich in plant material […]