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  • Title: Effect of penbutolol on lidocaine kinetics.
    Author: Ochs HR, Skanderra D, Abernethy DR, Greenblatt DJ.
    Journal: Arzneimittelforschung; 1983; 33(12):1680-1. PubMed ID: 6686773.
    Abstract:
    The effect of penbutolol (Betapressin), a stereospecific beta-adrenergic antagonist, on the pharmacokinetics of a single dose of intravenous lidocaine was evaluated in seven healthy volunteers. Subjects received a single 100-mg lidocaine intravenous dose of lidocaine hydrochloride, once in the control state and a second time during coadministration of penbutolol, 60 mg daily. Lidocaine volume of distribution was significantly increased during penbutolol treatment (4.9 vs 3.4 l/kg, p less than 0.005), resulting in a significant prolongation of elimination half-life (2.5 vs 2.0 h, p less than 0.025). The mechanism of the distributional shift is not established, but may result from a change in the pattern of peripheral blood flow and therefore the profile of tissue uptake of lidocaine. Total metabolic clearance of lidocaine, however, was not significantly altered by penbutolol (23.0 vs 19.4 ml/min/kg). The present study of healthy volunteers suggests that penbutolol increases lidocaine volume of distribution. If the finding also applied to patients, a higher loading dose of lidocaine might be necessary.
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