Identification of Drug Interactions

Most pharmacokinetic drug-drug interactions involve the effect of a drug on the cytochrome P450-mediated metabolism of another agent (Sandson et al. 2005). For these interactions to have clinical importance, the drug needs to have a narrow therapeutic index and only one primary P450 enzyme involved in its metabolism. The metabolism of drugs that are substrates of multiple cytochrome P450 enzyme subfamilies is not usually altered to a clinically significant degree by the inhibition of one P450 enzyme because metabolism can proceed through the remaining unaffected metabolizing enzymes.

The practitioner should remain mindful of the potential for significant P450-mediated interactions when a new drug is introduced to an estab lished medication regimen. Drugs with a narrow therapeutic index that are metabolized through a single P450 pathway are particularly vulnerable to such interactions. The addition or removal of drugs that inhibit or induce cytochrome P450 enzyme activity might require substrate dosage adjustments to maintain clinical efficacy and minimize potential toxic side effects. Clinical monitoring for signs of treatment-emergent toxicity and, when possible, laboratory monitoring of drug levels are both elements of safe clinical practice when the risk of drug interactions is suspected.

Drug interactions that affect renal elimination are important when an active drug is excreted primarily through the kidneys. Changes in urine pH may modify elimination of specific drugs. For example, drugs such as antacids that alkalinize the urine may reduce the excretion of drugs such as amphetamines and TCAs.

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