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Pharmacokinetics and Tissue Distribution of clevidipine and Its Metabolite in Dogs and Rats

Journal of Huazhong University of Science and Technology(Medical Sciences) 2014年第6期34卷 856-860页

作者：周莹何晓梦李虎群倪扬许明珍谌辉黎维勇 Institute of Clinic Pharmacy Union Hospital Tongji Medical College Huazhong University of Science and Technology

The purpose of the current study was to examine the pharmacokinetic profiles and tissue distribution of clevidipine, an ultra-short-acting calcium antagonist in Beagle dogs and Sprague-Dawley rats, respectively. The pharmacokinetics and biodistribution of its primary metabolite H 152/81 were also evaluated. Dogs received intravenous infusion of clevidipine at a dose rate of 17 μg/（kg·min）, and rats were given intravenous administration of clevidipine at a dose of 5 mg/kg. Dog plasma and rat tissues were collected and assayed by HPLC-MS/MS. It was found that plasma clevidipine quickly reached the steady state concentration. The terminal half-life was short （16.8 min）, pointing out a rapid elimination after the end of the infusion. The total clearance was 5 mL/（min·kg）. In comparison, plasma concentra- tion of H152/81 was increased more slowly and was significantly higher than that of clevidipine. After intravenous administration, clevidipine was distributed rapidly into all tissues examined, with the high- est concentrations found in the brain, heart and liver. Maximal concentrations of clevidipine were found in most tissues at 10 min post-dosing. However, the proportion of clevidipine distributed in all tissues was quite small （0.042‰） compared to the total administration dose. It was suggested that clevidipine was mainly distributed in blood and it transformed to inactive metabolite raoidlv.

关键词： pharmacokinetics tissue distribution clevidipine metabolite

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Management of hypertensive crises in the elderly

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Journal of Geriatric Cardiology 2018年第7期15卷 514-522页

作者： Abbas Alshami Carlos Romero America Avila Joseph Varon Dorrington Medical Associates Houston Texas USA University of Baghdad/College of Medicine Baghdad Iraq Universidad Autonoma de San Luis Potosi San Luis Potosi Mexico Universidad Durango Santander Hermosillo Sonora Mexico The University of Texas Health Science Center at Houston USA The University of Texas Medical Branch at Galveston USA Critical Care Services United Memorial Medical Center / United General Hospital Houston Texas USA

Hypertensive crises are elevations of blood pressure higher than 180/120 mmHg. These can be urgent or emergent, depending on the presence of end organ damage. The clinical presentation of hypertensive crises is quite variable in elderly patients, and clinicians must be suspicious of non-specific symptoms. Managing hypertensive crises in elderly patients needs meticulous knowledge of the pathophysiological changes in them, pharmacological options, pharmacokinetics of the medications used, their side effects, and their interactions with other medications. clevidipine, nicardipine, labetalol, esmolol, and fenoldopam are among the preferred choices in the elderly due to their efficacy and tolerability. Nitroprusside, hydralazine, and nifedipine should be avoided, unless there are no other options available, due to the high risk of complications and unpredictable responses.

关键词： Beta-blockers Calcium channel blockers clevidipine Elderly Esmolol Fenoldopam Hypertensive crises Labetalol Nicardipine Nitroprusside

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Diagnosis and treatment of hypertensive crises in the elderly patients

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Journal of Geriatric Cardiology 2007年第1期4卷 50-55页

作者： Joseph Varon Neil E. Strickman University of Texas Health Science Center at Houston Houston Texas USA Peripheral Vascular Lab at HGCA Peripheral Vascular Interventional Cardiology at Texas Heart Institute / St Lukes Episcopal Hospital Houston Texas USA

Hypertension is a common clinical problem in the elderly worldwide and physicians of all types are likely to encounter patients with hypertensive urgencies and emergencies in these patients. Although various terms have been applied to these conditions, they are all characterized by acute elevations in blood pressure and evidence of end-organ injury. Prompt, but carefully considered therapy is necessary to limit morbidity and mortality. A wide range of pharmacologic alternatives are available to the practitioner to control blood pressure and treat complications in these patients. The management of the elderly patient with hypertensive crises needs to include close monitoring and a gentle decline in blood pressure to avoid catastrophic complications, exacerbation of ischemic myopathy, and vascular insufficiency.

关键词： hypertension hypertensive crises hypertensive encephalopathy aortic dissection beta-blocker calcium channel blocker clevidipine fenoldopam nitroprusside labetalol nicardipine elderly

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