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 p...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.展开更多
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 hav...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.展开更多
基金supported in part by the Important National Science & Technology Specific Projects in the 12th Five-year Plan of China(No.2011ZX09302-002-01)
文摘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.
文摘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.
