• William B Smith, Thomas C Marbury, Steven F Komjathy, Mark S Sumeray, Gregory C Williams, Ming-yi Hu, and Diane R Mould.
• Volunteer Research Group, University of Tennessee Medical Center, Knoxville, TN, USA.
• Eur. J. Clin. Pharmacol. 2012 Oct 1;68(10):1385-94.

PurposeClevidipine is a rapidly-acting intravenous dihydropyridine antihypertensive acting via calcium channel blockade. This was a randomized, single-blind, parallel-design study of a 72-h continuous clevidipine infusion.MethodDoses of 2, 4, 8, or 16.0 mg/h or placebo were evaluated in 61 subjects with mild to moderate essential hypertension. IV clevidipine or placebo was initiated at 2.0 mg/h and force-titrated in doubling increments every 3 min to target dose, then maintained for 72 h. Blood pressure and heart rate were measured during infusion, and for 4, 6 and 8 h after termination of infusion, although oral therapy could be restarted at 4 h. Clevidipine blood levels were obtained during infusion and for 1 hour after termination.ResultsRapid onset of drug effect occurred at all clevidipine dose levels, with consistent pharmacokinetics and rapid offset after 72-h infusion. No evidence of tolerance to the clevidipine drug effect was observed at any dose level over the 72-h infusion. No evidence of rebound hypertension was found for either 4 or 6 h after termination of the clevidipine infusion. At 8 h following cessation of clevidipine, blood pressure was not significantly higher than at baseline. Placebo-treated subjects had blood pressures lower than baseline at 8 h following infusion termination; hence, placebo-adjusted blood pressures tended to be slightly higher than baseline.ConclusionThis study supports the use of up to 72 h of IV clevidipine therapy for the management of blood pressure, with consistent pharmacokinetic/pharmacodynamic characteristics and context insensitive half-life across the dose ranges evaluated.

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