title: Effect of selective cyclooxygenase-2 inhibitors on heart rate in healthy young men.
abstract: During an investigation of the possible pharmacokinetic interactions of cyclooxygenase-2 (COX-2) inhibitors with metoprolol, we observed that rofecoxib caused a significant reduction in heart rate in young healthy volunteers. The effect of valdecoxib did not reach significance. When these drugs were given together with metoprolol, the effect was continued. The latter effect could not be related to pharmacokinetic interactions. In the light of experimental results claiming a cardioprotective effect of possibly COX-2-derived prostaglandins and clinical observations hinting at an increased risk of sudden cardiovascular death in conjunction with the long-term use of selective cyclooxygenase inhibitors, our results may help to increase awareness and to suggest investigation of the impact of coxibs on heart function.
authors.affiliation: Department of Experimental and Clinical Pharmacology and Toxicology, FAU Erlangen-Nuremberg, Erlangen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Lamprecht
authors.forename: Ulrike
authors.initials: U
authors.lastname: Werner
authors.forename: Dierk
authors.initials: D
authors.lastname: Werner
authors.forename: Simon
authors.initials: S
authors.lastname: Schaefer
authors.forename: Bertold
authors.initials: B
authors.lastname: Renner
authors.forename: Martin
authors.initials: M
authors.lastname: Fromm
authors.forename: Kay
authors.initials: K
authors.lastname: Brune
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004338:Drug Combinations; D004347:Drug Interactions; D015716:Electrocardiography, Ambulatory; D006321:Heart / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D008790:Metoprolol / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D012016:Reference Values; D013412:Sulfadimethoxine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D000319:Adrenergic beta-Antagonists; D016861:Cyclooxygenase Inhibitors; D004338:Drug Combinations; D007555:Isoxazoles; D008790:Metoprolol; D011743:Pyrimidines; D013412:Sulfadimethoxine; D013449:Sulfonamides; C003275:ormetoprim, sulfadimethoxine drug combination; C406224:valdecoxib; D000096926:Benzenesulfonamides