Pharmacokinetics and pulmonary extraction of clevidipine, a new vasodilating ultrashort-acting dihydropyridine, during cardiopulmonary bypass †

Vuylsteke, Alain; Milner, Q. J. W.; Ericsson, Henrik; Mur, Daniel Sagarra; Dunning, John; Jolin‐Mellgård, Å.; Nordlander, Margareta; Latimer, R.D.

doi:10.1093/bja/85.5.683

Cited by 19 publications

(19 citation statements)

References 28 publications

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“…In contrast, there was no lag time in arterial blood collected from the left radial artery in patients undergoing CABG surgery (53). The presence of an arteriovenous concentration difference was verified when arterial and venous blood samples were collected in healthy volunteers who received clevidipine infusions for up to 24 h (14) (Fig.…”

Section: Pharmacokineticsmentioning

confidence: 93%

“…Three of these studies were conducted postoperatively (7,31,44) and two were performed perioperatively (2,53).…”

Section: Studies In Patients Undergoing Cardiac Surgerymentioning

confidence: 99%

“…The dose of clevidipine required to control blood pressure before and during cardiopulmonary bypass (CPB) was compared in 8 patients during CABG surgery (53). The infusion rate of clevidipine needed to reduce MAP to the required level during the pre-bypass stage (normothermic) was two times the infusion rate required during bypass (hypothermic) conditions.…”

Section: Perioperative Studies In Cardiac Surgery Patientsmentioning

confidence: 99%

“…All patients recovered completely. Twenty-seven patients of the 212 patients in the program undergoing cardiac surgery experienced a total of 53 serious adverse events (2,7,31,35,53) but only one of these events (7) was considered as possibly related to clevidipine.…”

Section: Adverse Eventsmentioning

confidence: 99%

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Pharmacodynamic, Pharmacokinetic and Clinical Effects of Clevidipine, an Ultrashort‐Acting Calcium Antagonist for Rapid Blood Pressure Control

Nordlander

Sjöquist

Ericsson

et al. 2004

Cardiovascular Drug Reviews

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Clevidipine 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.

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Section: Pharmacokineticsmentioning

confidence: 93%

“…Three of these studies were conducted postoperatively (7,31,44) and two were performed perioperatively (2,53).…”

Section: Studies In Patients Undergoing Cardiac Surgerymentioning

confidence: 99%

Section: Perioperative Studies In Cardiac Surgery Patientsmentioning

confidence: 99%

Section: Adverse Eventsmentioning

confidence: 99%

See 2 more Smart Citations

Pharmacodynamic, Pharmacokinetic and Clinical Effects of Clevidipine, an Ultrashort‐Acting Calcium Antagonist for Rapid Blood Pressure Control

Nordlander

Sjöquist

Ericsson

et al. 2004

Cardiovascular Drug Reviews

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“…These compounds have an important role in the cardiovascular system, such as controlling arterial blood pressure [1].…”

Section: Introductionmentioning

confidence: 99%

Felodipine quantification in human plasma by high-performance liquid chromatography coupled to tandem mass spectrometry

Migliorança

Barrientos‐Astigarraga²,

Schug

et al. 2005

Journal of Chromatography B

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Enantioselective pharmacokinetics of the enantiomers of clevidipine following intravenous infusion of the racemate in essential hypertensive patients

et al. 2001

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The aim of the study was to characterize the individual pharmacokinetics of (-)-R- and (+)-S-clevidipine following intravenous constant rate infusion of rac-clevidipine to essential hypertensive patients. Twenty patients received three out of five randomized treatments with clevidipine. The pharmacokinetics of the separate enantiomers were evaluated by compartmental analysis of blood concentrations vs. time curves using the population approach. The derived pharmacokinetic parameters were used to simulate the time for 50 and 90% postinfusion decline following various infusion times of rac-clevidipine. A two-compartment model was used to describe the dispositions of the enantiomers; there were only minor differences between the estimated pharmacokinetic parameters of the separate enantiomers. The mean blood clearance values of (-)-R- and (+)-S-clevidipine were 0.103 and 0.096 l/min/kg, and the corresponding volumes of distribution at steady state were 0.39 and 0.54 l/kg, respectively. The context-sensitive half-time was approximately 2 min regardless of stereochemical configuration, and a 90% decline in concentration was achieved approximately 8 min postinfusion for (-)-R-clevidipine and 11 min for (+)-S-clevidipine, following clinically relevant infusion times with clevidipine. In conclusion, both enantiomers are high-clearance compounds with similar blood clearance values. The volume of distribution for the enantiomers is slightly different, presumably due to differences in the protein binding. From a pharmacokinetic point of view, the use of a single enantiomer as an alternative to the racemic clevidipine will not offer any clinical advantages.

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Pharmacokinetics and pulmonary extraction of clevidipine, a new vasodilating ultrashort-acting dihydropyridine, during cardiopulmonary bypass †

Cited by 19 publications

References 28 publications

Pharmacodynamic, Pharmacokinetic and Clinical Effects of Clevidipine, an Ultrashort‐Acting Calcium Antagonist for Rapid Blood Pressure Control

Pharmacodynamic, Pharmacokinetic and Clinical Effects of Clevidipine, an Ultrashort‐Acting Calcium Antagonist for Rapid Blood Pressure Control

Felodipine quantification in human plasma by high-performance liquid chromatography coupled to tandem mass spectrometry

Enantioselective pharmacokinetics of the enantiomers of clevidipine following intravenous infusion of the racemate in essential hypertensive patients

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