Itraconazole markedly increased bioavailability of celiprololand only slightly affected pharmacokinetics of atenolol, without affecting heart rate or blood pressure These interactions arenot expected to be clinically relevant.
Clinical evidence,mechanism, importance and management
In a study in 10 healthy subjects itraconazole 200mg twice daily for 5 doses had only minor effects on pharmacokinetics of a single 50mg dose of atenolol and no effects on heart rate or blood pressure were seen (See reference number 1)
In a study in 12 healthy subjects itraconazole 200mg twice daily for 5 doses increased AUC of a single 100mg dose of celiprolol by 80%, without increasing half-life. However, itraconazole did not increase effect of celiprolol on heart rate or blood pressure (See reference number 2).
It was suggested that itraconazole probably increases absorption of celiprolol by inhibiting P-glycoprotein in intestinal wall (See reference number 2)
Although increase in plasma levels was marked, it was suggested that it is unlikely to be clinically relevant because celiprolol has a wide therapeutic range (See reference number 2).
Lilja JJ,Backman JT, Neuvonen PJ. Effect of itraconazole on the pharmacokinetics of atenolol.Basic Clin Pharmacol Toxicol (2005) 97, 395–8.
Lilja JJ,Backman JT, Laitila J, Luurila H, Neuvonen PJ. Itraconazole increases but grapefruitjuice greatly decreases plasma concentrations of celiprolol. Clin Pharmacol Ther (2003) 73, 192–8.