Why the study?
Does the addition of propranolol alter the pharmacokinetics of warfarin in healthy volunteers and rabbits?
Does the addition of propranolol alter the pharmacokinetics of warfarin in healthy volunteers and rabbits?
Propranolol alters the pharmacokinetics of warfarin, increasing its concentration in humans, which may be clinically important given warfarin's narrow therapeutic index.
May warrant INR monitoring with propranolol coadministration; leaves open the clinical significance of this pharmacokinetic interaction.
The interaction between propranolol and warfarin was investigated in six healthy volunteers using a low dose warfarin protocol and in New Zealand white rabbits. Warfarin concentration (Cmin) in the volunteers increased by 14.7% on addition of propranolol (P less than 0.02). There was no significant change in prothrombin time. In the rabbit study, elimination half-life was shorter in the propranolol treated animals (8.20 +/- 0.44 h) than in controls (10.89 +/- 0.62 h). This was due to a fall in its volume of distribution from 1.13 +/- 0.10 1 kg-1 in controls to 0.81 +/- 0.08 1 kg-1 in the propranolol treated group. Clearance was not significantly altered. The small change in warfarin concentration could be of clinical importance in some patients because warfarin has a low therapeutic index. This requires further investigation.
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Scott et al. (1984) studied this question.
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