title: Pharmacokinetics, pharmacodynamics, and safety of clevidipine after prolonged continuous infusion in subjects with mild to moderate essential hypertension.
abstract: OBJECTIVE
  Clevidipine 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.
  
  
  METHODS
  Doses 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.
  
  
  RESULTS
  Rapid 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.
  
  
  CONCLUSIONS
  This 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.
authors.affiliation: Volunteer Research Group, University of Tennessee Medical Center, Knoxville, TN, USA.
authors.forename: William B
authors.initials: WB
authors.lastname: Smith
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Marbury
authors.forename: Steven F
authors.initials: SF
authors.lastname: Komjathy
authors.forename: Mark S
authors.initials: MS
authors.lastname: Sumeray
authors.forename: Gregory C
authors.initials: GC
authors.lastname: Williams
authors.forename: Ming-yi
authors.initials: MY
authors.lastname: Hu
authors.forename: Diane R
authors.initials: DR
authors.lastname: Mould
mesh_terms: D000959:Antihypertensive Agents / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D004095:Dihydropyridines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006207:Half-Life; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D011725:Pyridines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D016037:Single-Blind Method
chemical_list: D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D011725:Pyridines; C118563:clevidipine