How does systemic ketoconazole affect salmeterol xinafoate exposure and the risk of side effects?

In a seven-day healthy-volunteer study, oral ketoconazole (400 mg daily) with inhaled salmeterol xinafoate (50 micrograms twice daily) increased salmeterol Cmax 1.4-fold and AUC 15-fold, potentially increasing systemic effects including QTc prolongation and palpitations; concomitant use should be avoided unless benefits outweigh risks.