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Pharmacodynamic, pharmacokinetic and clinical effects of clevidipine, an ultrashort-acting calcium antagonist for rapid blood pressure control Nordlander M; Sjoquist PO; Ericsson H; Ryden LCardiovasc Drug Rev 2004[Fal]; 22 (3): 227-50Clevidipine is an ultrashort-acting vasoselective calcium antagonist under development for short-term intravenous control of blood pressure. Studies in animals, healthy volunteers and patients have demonstrated the vascular selectivity and rapid onset and offset of antihypertensive action of clevidipine, a synthetic 1,4-dihydropyridine that inhibits L-type calcium channels. Clevidipine has a high clearance (0.05 L/min/kg) and is rapidly hydrolyzed to inactive metabolites by esterases in arterial blood. Its half-life in patients undergoing cardiac surgery is less than one min. Unlike sodium nitroprusside, a drug commonly used for the short-term control of blood pressure, which dilates both arterioles and veins, clevidipine reduces blood pressure through a selective effect on arterioles. As documented in animals and in cardiac surgical patients, clevidipine reduces peripheral resistance without any undesirable effect on cardiac filling pressure. It increases stroke volume and cardiac output. In anesthetized patients undergoing cardiac surgery clevidipine, unlike sodium nitroprusside, does not increase heart rate. In addition of having a favorable hemodynamic profile, suitable for rapid control of blood pressure, clevidipine protects against ischemia/reperfusion injuries, which are not uncommon during major surgery. In anesthetized pigs, clevidipine reduced infarct size after 45 min-long myocardial ischemia by 40%. In rats, renal function and splanchnic blood flow were better maintained when blood pressure was reduced with clevidipine than with sodium nitroprusside. Clevidipine was well tolerated in Phases I and II of clinical trials that included more than 300 individuals/patients. Since there are no known compounds with similar pharmacodynamic and pharmacokinetic properties in clinical development, it is anticipated that clevidipine, a compound tailored to the needs of anesthesiologists, has the potential to become a drug of choice for controlling blood pressure during surgical procedures.|Animals[MESH]|Blood Pressure/*drug effects[MESH]|Calcium Channel Blockers/pharmacokinetics/*pharmacology/*therapeutic use[MESH]|Cardiotonic Agents/pharmacokinetics/pharmacology/therapeutic use[MESH]|Clinical Trials as Topic[MESH]|Hemodynamics/drug effects[MESH]|Humans[MESH]|Hypertension/drug therapy/physiopathology[MESH]|Pyridines/pharmacokinetics/*pharmacology/*therapeutic use[MESH]|Reperfusion Injury/drug therapy/physiopathology[MESH]|Time Factors[MESH] |
