Effects of sustained intravenous diltiazem infusion in healthy persons

A 3-stage infusion of diltiazem was tested in 8 subjects for up to 48 hours: a bolus injection (10 mg over 3 minutes), a rapid loading infusion (20 mg over 30 minutes) and a maintenance infusion (10 mg/hour to the end of the study). This regimen produced stable median plasma diltiazem concentrations of approximately 150 ng/ml. The median half-life of elimination for diltiazem was 206 minutes (range 144 to 452) and median total clearance was 980 ml/min (range 665 to 1,907). The PR interval lengthened 10 to 18% during the maintenance infusion in 7 subjects; in 1 subject atrioventricular nodal Wenckebach conduction was recorded during the rapid loading infusion. Systolic blood pressure decreased from 124 ± 7 mm Hg (mean ± standard deviation) during the control period to 121 ± 8 mm Hg during the rapid loading infusion (p = 0.03 compared with control) and to 117 ± 7 mm Hg (p = 0.04 compared with control) during the maintenance infusion. Heart rate did not change. PR interval and blood pressure returned to control levels within 4 hours after the infusion was stopped. Loading and maintenance infusion may be an attractive method of administering diltiazem when stable drug concentrations are required for prolonged periods.