Bisoprolol: studies of potential interactions with theophylline and warfarin in healthy volunteers.
Many patients receiving bisoprolol treatment might also require warfarin or theophylline therapy. Two studies were carried out in healthy volunteers to investigate the possibility that bisoprolol might interact with warfarin or theophylline, both of which have low therapeutic ratios. In a balanced, two-way, crossover study, eight men and four women took bisoprolol 10 mg daily for 14 days. They were divided into two groups of six volunteers. On the tenth day of treatment, six subjects received theophylline 375 mg (Nuelin tablets) by mouth and the pharmacokinetics of theophylline were determined. After a washout period of 7 days, they also underwent determination of single-dose theophylline kinetics. The other six subjects had single-dose theophylline kinetics determined 7 days before the first dose of bisoprolol, and then again after 10 days of bisoprolol treatment. Concurrent administration of bisoprolol did not influence the tolerability of theophylline and had no significant effect on any of the pharmacokinetic parameters for theophylline. In a separate study, 12 healthy men received warfarin daily until their prothrombin times were about 1.5 x control. They then received bisoprolol 10 mg daily p.o. for 10 days; warfarin was continued until 5 days after the end of bisoprolol treatment. Bisoprolol and warfarin treatments were well tolerated, and there was no effect on prothrombin times of either starting or stopping bisoprolol treatment. These studies show no effect of bisoprolol treatment upon theophylline pharmacokinetics, and no evidence of an effect of bisoprolol upon low-level anticoagulation with warfarin. Nevertheless, care should always be taken when changes are made in the medication of patients receiving theophylline or warfarin.
Warrington
S J
SJ
Charterhouse Clinical Research Unit Limited, St. Bartholomew's Hospital, London, England.
Johnston
A
A
Lewis
Y
Y
Murphy
M
M
D000319:Adrenergic beta-Antagonists / Q000097:blood / Q000493:pharmacokinetics*; D000328:Adult; D000925:Anticoagulants / Q000097:blood / Q000493:pharmacokinetics*; D017298:Bisoprolol / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004347:Drug Interactions / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011517:Prothrombin Time; D013806:Theophylline / Q000097:blood / Q000493:pharmacokinetics*; D014665:Vasodilator Agents / Q000097:blood / Q000493:pharmacokinetics*; D014859:Warfarin / Q000097:blood / Q000493:pharmacokinetics*
D000319:Adrenergic beta-Antagonists; D000925:Anticoagulants; D014665:Vasodilator Agents; D014859:Warfarin; D013806:Theophylline; D017298:Bisoprolol