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Therefore, it is not expected that an increase of either bosentan or sildenafil exposure towards higher concentrations would lead to improved efficacy. The key finding that imatinib increased co‐medication exposure immediately raises the question whether the efficacy of imatinib is caused by enhancing the effect of bosentan and sildenafil via increasing their exposure. As bosentan concentrations were, on average, roughly doubled in the presence of sildenafil and imatinib, the next question to be answered was the clinical relevance of this increased exposure. Erectile function was subjectively assessed with the IIEF‐5 questionnaire and response to the global efficacy question (GEQ). Gokkaya and colleagues (2008) evaluated the effect of correction of serum cholesterol levels on erectile function and sildenafil treatment in patients with ED who have only hypercholesterolemia as a risk factor for ED. Compared with placebo, quinapril improved symptoms of ED significantly, as measured by the International Index of Erectile Function 5 (IIEF‐5) questionnaire. Another study evaluated the effects of adjunctive treatment with atorvastatin or the antihypertensive quinapril (an angiotensin converter enzyme inhibitor) in men with vasculogenic ED who were suboptimal responders to 100 mg of sildenafil. Interestingly, the effects of bosentan and imatinib on sildenafil cancelled out, bringing exposure close to that observed in the absence of both the drugs.
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