PT  - JOURNAL ARTICLE
AU  - J E Chelly
AU  - D C Hill
AU  - D R Abernethy
AU  - A Dlewati
AU  - M F Doursout
AU  - R G Merin
TI  - Pharmacodynamic and pharmacokinetic interactions between lidocaine and verapamil.
DP  - 1987 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 211--216
VI  - 243
IP  - 1
4099  - http://jpet.aspetjournals.org/content/243/1/211.short
4100  - http://jpet.aspetjournals.org/content/243/1/211.full
SO  - J Pharmacol Exp Ther1987 Oct 01; 243
AB  - Lidocaine (3 mg/kg i.v.) injected during steady-state verapamil infusions (3 micrograms/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 micrograms/kg/min) in the presence of steady-state verapamil (200 micrograms/kg over 3 min followed by 3 micrograms/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).