Drug interactions - Distribution

Distribution interactions occur when drugs are extensively protein-bound and the co-administration of a second can displace it to the non-bound active form. This increases the amount of (unbound) drug available to cause an effect. For example, diazepam displaces phenytoin from plasma proteins, resulting in an increased plasma concentration of free phenytoin and an increased risk of toxicity. The effects of protein displacement are usually short-lived because the metabolism of the affected drug usually increases in parallel with the increased free drug concentration. Distribution interactions can however be significant for drugs that have extremely rapid distribution or narrow therapeutic indices, such as lithium or digoxin.