Pharmacokinetics and pharmacodynamics of clevidipine in healthy volunteers after intravenous infusion

Ericsson, Henrik; Fakt, Christina; Höglund, Lena; Jolin‐Mellgård, Å.; Nordlander, Margareta; Sunzel, Maria; Regårdh, C G

doi:10.1007/s002280050594

Cited by 50 publications

(45 citation statements)

References 16 publications

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“…This metabolite is subsequently metabolized to a large extent by glucuronidation, oxidation or decarboxylation before excretion. The pharmacokinetics of the main metabolite, with a terminal half-life of approximately 9 h, differs markedly from clevidipine (15,16 administration of tritium-labeled clevidipine suggests biliary elimination and /or intestinal secretion of clevidipine and/or its metabolites (15).…”

Section: Metabolismmentioning

confidence: 98%

“…However, characterizing pharmacokinetics of a drug with disposition models containing two or three exponential phases with different half-lives is sometimes done by arbitrary judgments. The important phases in describing the pharmacokinetic properties of clevidipine are those immediately after cessation of the infusion, since the initial rapid post-infusion decline in clevidipine levels is primarily related to elimination (15). Thus, use of decremental times rather than different half-lives is more appropriate for describing the pharmacokinetics of clevidipine.…”

Section: Half-life and Decrement Timesmentioning

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: Metabolismmentioning

confidence: 98%

Section: Half-life and Decrement Timesmentioning

confidence: 99%

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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show abstract

“…The ideal perioperative antihypertensive agent would have rapid onset and short duration of activity with easy titration to effect and a low risk of overshoot hypotension [42]. The benefits and limitations of currently used agents are summarized in tables 3 and 4[29,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75]. Where available, comparison studies have been included; however, it should be noted that rigorous studies involving commonly used antihypertensives are few and far between and, with the exception of the ECLIPSE program, were completed more than a decade ago.…”

Section: Traditional Therapies For Perioperative Hypertension: Meritsmentioning

confidence: 99%

Acute Kidney Injury following Cardiac Surgery: Role of Perioperative Blood Pressure Control

et al. 2011

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Background/Aims: Patients who develop acute kidney injury (AKI) after cardiac surgery continue to have a high mortality rate. Although factors that predispose to postoperative renal dysfunction have been identified, this knowledge has not been associated with a substantial reduction in the incidence of this serious adverse event. Methods: This review uses the existing literature to explore the relationship between AKI and perioperative blood pressure (BP) control in cardiac surgery patients. The results of recent novel analyses are introduced, and the implications of these studies for the management of cardiac surgery patients in the perioperative period are discussed. Results: Preexisting isolated systolic hypertension and wide pulse pressure increase the risk of postoperative renal dysfunction in the cardiac surgery population. New data suggest that BP lability (i.e., BP excursions outside an acceptable physiologic range) during cardiac surgery may also be an important predictor of subsequent renal dysfunction. Conclusion: Recently published data suggest that perioperative BP lability influences both the risk of postoperative renal dysfunction and 30-day mortality. Future studies will determine whether the use of agents that allow improved BP control within a desirable range will reduce the incidence of postoperative AKI in cardiac surgery patients.

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“…In two pharmacodynamic evaluations in healthy volunteers, clevidipine resulted in increases in heart rate by approximately 40% (from 59 to 82 bpm and from 53 to 75 bpm). 19,21 In both studies, heart rate returned to baseline values within 10 to 15 minutes after discontinuation of the infusion. 19,21 In ESCAPE-1, patients in both the clevidipine and placebo groups experienced increases in heart rate from a baseline of 71 and 76 bpm respectively to a maximum heart rate of 84 bpm in both groups.…”

Section: Adverse Effectsmentioning

confidence: 95%

“…Initial pharmacokinetic studies showed a mean blood clearance of 0.14 L/min/kg and a volume of distribution at steady state of 0.6 L/kg. 19 Clevidipine is highly protein-bound in humans (∼99.7%).…”

Section: Pharmacokinetic and Metabolism Profile Of Clevidipinementioning

confidence: 99%

Safety and Efficacy of Intravenous Clevidipine for the Perioperative Control of Acute Hypertension

Murphy

Brower

2011

Clinical Medicine Insights: Therapeutics

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Clevidipine is a third generation dihydropyridine calcium channel blocker recently approved by the Food and Drug Administration and is an emerging option for management of perioperative hypertension. This intravenous medication has several properties that may be advantageous when rapid and safe blood pressure control is required, including fast onset, short duration of action and the lack of renal or hepatic metabolism. Clevidipine has been demonstrated to be safe and efficacious for the management of perioperative hypertension in the cardiac surgery population, with minimal excursions outside of the target blood pressure range. Despite the fact that clevidipine does have certain advantages over alternative agents, it has some distinct limitations associated with its use, including higher associated costs and limited data in non-cardiac surgery patients. While clevidipine may serve as an additional option, further research is required to fully establish the role of clevidipine in the management of perioperative hypertension.

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Pharmacokinetics and pharmacodynamics of clevidipine in healthy volunteers after intravenous infusion

Cited by 50 publications

References 16 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

Acute Kidney Injury following Cardiac Surgery: Role of Perioperative Blood Pressure Control

Safety and Efficacy of Intravenous Clevidipine for the Perioperative Control of Acute Hypertension

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