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These interactions involve interference with absorption, distribution or metabolism of one drug as a consequence of the administration of another. They tend to be less easy to predict than pharmacodynamic interactions, although the consequences may be no less severe. Some commonly encountered pharmacokinetic interactions are summarised in Table 4.2.

Table 4.2 Examples of pharmacokinetic interactions.

Absorption interactions

Tetracyclines chelate calcium, iron and magnesium salts leading to reduced antibiotic absorption

Cholestyramine reduces warfarin absorption by binding to it

Distribution interactions

Aspirin displaces warfarin from plasma proteins, potentiating the anti‐coagulant effect

Meropenem displaces valproate from its protein binding sites leading to greatly increased clearance of valproate and rapid loss of effect

Metabolism interactions

Induction

Carbamazepine induces enzymes which metabolise phenytoin, necessitating larger doses of phenytoin

The antibiotic rifampicin is a potent inducer of many enzymes involved in drug metabolism and causes many troublesome pharmacokinetic drug interactions

Inhibition

Macrolide antibiotics such as clarithromycin inhibit metabolic enzymes in the liver leading to increased drug levels of many drugs including many statins such as simvastatin

Allopurinol potentates the cytotoxic effect of azathioprine by inhibiting xanthine oxidase, the enzyme responsible for its enzymatic degradation

An exhaustive list of all potential interactions lies out with the scope of this text. Appendix 1 of the BNF provides a useful reference, and should be consulted whenever the question of a potential interaction arises.