Enzyme Induction CYP3A4 and Drug Design

In contrast to these concentrations many clinically-used drugs, which are non-inducers are effective at doses up to two orders of magnitude lower. The need for high doses has other undesirable complications. As outlined above dose size is important in toxicity and enzyme inducers show a high level of adverse drug reactions affecting such organs and tissues as the liver, blood and skin (Table 8.4). 

This statement is somewhat at odds with the conventional view that idiosyncratic toxicology is dose-size independent. Idiosyncratic reactions are thought to result from an immune-mediated cell injury triggered by previous contact with the drug. The toxicity may appear after several asymptomatic administrations of the com- 

Carbamazepine Aplastic anaemia, agranulocytosis, skin rash, hepatitis 

Rifampicin Shock, haemolytic anaemia, renal failure 

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Enzyme Induction (CYP3A4) and Drug Design 1119 Tab. 8.4 Clinical toxicities and side-effects of P4503A4 inducers. 

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