How Common Are Drug and Gene Interactions?

How Common Are Drug and Gene Interactions?

Results

Data from 1190 individuals was analyzed with 47 individuals excluded because of age. Of the remaining 1143 individuals, the ages ranged from 18 years to 89 years with a mean ± SD age of 60 (±15) years. The total number of medications ranged from 1 to 44, with a mean of 8.4 (±5.7) medications and a median of seven medications. Six hundred and forty-two individuals with little potential for interactions (defined as no, or minimal, or moderate interaction according to our categories) had a mean ± SD age of 60 (±14.8) years. The mean medication count for this group was 6.5 (±4.5) with a median of five medications.

We found that 31% (357/1143) of individuals had a DDI, 12% (138/1143) had a DGI and 12% (137/1143) had a DDGI. Individuals with potentially significant interactions (defined as a major or substantial interaction according to our categories) represented nearly half of the dataset (501 individuals or 44% of the total). Some individuals were found to have both a DDI and a DGI or DDGI, and patients averaged a total of 2.1 interactions. The mean age ± SD of individuals with these interactions was 61 (±15) years. The mean medication count ± SD of individuals with a major or significant interaction was 11.0 (±6.0), with a median of ten medications.

We identified 1053 major or substantial interactions in the 501 individuals with potentially significant interactions. Each patient had on average 2.1 major or substantial interactions. The results are summarized in Table 3 based on type of interaction. DGIs represented 14.7% of all interactions and DDGIs represented 19.2% for a total of 33.9% of all interactions. The remaining interactions (66.1%) were DDIs.

When limited only to the patients with major interactions, the relative representation of the three types of interactions, DDI, DGI and DDGI, is similar to major and substantial interactions. When considering only major interactions, DGIs represent 13.9% of all interactions, and DDGIs represented 21.5% of all interactions – a total of 35.4% of all interactions. The remaining interactions (64.6%) were DDIs. Figure 2 displays the interactions by interaction category. Adding the DGI and DDGI interactions together yields the total number of interactions associated with genetic polymorphisms. This represents a 51.3% increase (1053 vs 696) of major or substantial interactions above the prevalence of DDIs alone. When considering major interactions only, there is a 54.9% (525 vs 339) increase of genetic interactions above DDIs.


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Figure 2.

Frequency of drug–drug, drug–gene and drug–drug–gene interactions predicted.
DDI: Drug–drug interaction; DDGI: Drug–drug–gene interaction; DGI: Drug–gene interaction.

Medications most frequently involved in major interactions were metoprolol, clopidogrel, simvastatin, aspirin and hydrocodone. These medications included both victim and perpetrators and were involved in either pharmacokinetic or pharmacodynamic interactions. The most common medication classes causing major interactions include β-adrenergic blocking agents, antidepressants, antiplatelets, opioid analgesics and anti-inflammatory agents (Table 4 & Table 5).