Pharmacodynamic and pharmacokinetic interactions between lidocaine and verapamil

J. E. Chelly, D. C. Hill, D. R. Abernethy, A. Dlewati, M. F. Doursout, R. G. Merin

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Abstract

Lidocaine (3 mg/kg i.v.) injected during steady-state verapamil infusions (3 μg/kg i.v.) induced slight and transient hemodynamic changes in nine conscious dogs. Systemic vascular resistance and left ventricular dP/dt decreased by 16% from 41 ± 4 mm Hg/liter/min and by 20% from 2876 ± 137 mm Hg/sec, respectively, whereas heart rate and cardiac output increased by 18% from 100 ± 5 beats/min and by 17% from 2.5 ± 0.2 liters/min, respectively. Simultaneously, lidocaine induced a transient but more pronounced decrease in verapamil plasma concentration of 48% from 60 ± 3 ng/ml. This pharmacokinetic interaction was not the result of a lidocaine-induced decrease in the fraction of verapamil bound to plasma protein because in vitro lidocaine failed to displace verapamil from its protein binding site. Moreover, an increase in verapamil total clearance was not the only mechanism because steady-state lidocaine (6 mg/kg over 5 min followed by 60 μg/kg/min) in the presence of steady-state verapamil (200 μg/kg over 3 min followed by 3 μg/kg/min) also resulted in a transient decrease in verapamil plasma concentration from 59 ± 9 to 23 ± 2 ng/ml in six conscious dogs. Although verapamil did not affect lidocaine pharmacokinetics, in the presence of the steady-state lidocaine we recorded an increase in verapamil initial volume of distribution of 44% from 40 ± 4 liters, and intercompartmental clearance increased by 88% from 101 ± 20 liters/hr, combined with an increase in verapamil total clearance of 47% from 54 ± 6 liters/hr (n = 6).

Original languageEnglish (US)
Pages (from-to)211-216
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume243
Issue number1
StatePublished - Jan 1 1987

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ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Chelly, J. E., Hill, D. C., Abernethy, D. R., Dlewati, A., Doursout, M. F., & Merin, R. G. (1987). Pharmacodynamic and pharmacokinetic interactions between lidocaine and verapamil. Journal of Pharmacology and Experimental Therapeutics, 243(1), 211-216.