Role of isoflurane on hemodynamic properties and disposition of nicardipine.

J. E. Chelly, E. S. Hysing, D. R. Abernethy, M. F. Doursout, C. J. Hartley, M. Guerret, R. G. Merin

Research output: Contribution to journalArticlepeer-review

Abstract

Nicardipine properties (30 micrograms/kg i.v.) were studied in a group of eight dogs awake and anesthetized with isoflurane 1.6% end-tidal. Awake, nicardipine produced a decrease in mean arterial pressure (-12 +/- 2 mm Hg) associated with an increase in cardiac output (1.63 +/- 0.2 liters/min), heart rate (75 +/- 9 beats/min), dP/dt (741 +/- 202 mm Hg/sec) and carotid (41 +/- 11 ml/min) and coronary blood flows (39 +/- 6 ml/min). During isoflurane, responses to nicardipine injections were less pronounced except for mean arterial pressure (-19 +/- 2 mm Hg) and reversed for dP/dt (-290 +/- 63 mm Hg/sec). In a second group of six conscious dogs, nicardipine (30 micrograms/kg i.v.) injected after ganglionic blockade (chlorisondamine, 2 mg/kg i.v.) elicited changes similar to those recorded during isoflurane anesthesia, data that demonstrated the importance of isoflurane-induced baroreflex blockade as a mechanism of the pharmacodynamic interactions between nicardipine and isoflurane. Isoflurane reduced nicardipine initial volume of distribution (11.6 +/- 1.2 vs. 8.9 +/- 0.8 liters), total clearance (28.5 +/- 2.9 vs. 19.2 +/- 2.1 liters/hr) and volume of distribution at steady state (50.0 +/- 11.3 vs. 29.2 +/- 3.7 liters, P less than .05). Nicardipine-induced hemodynamic changes were linearly correlated with the drug concentrations in plasma. In the presence of isoflurane, the slopes of these relationships were reduced for all hemodynamic variables except for mean arterial pressure, for which the slope was more pronounced, and dP/dt, for which the slope was reversed. In conclusion, isoflurane alters the drug plasma concentration-effect relationship of nicardipine as a result of both pharmacokinetic and pharmacodynamic interactions.

Original languageEnglish (US)
Pages (from-to)899-906
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume241
Issue number3
StatePublished - Jun 1 1987

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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