Preclinical Development for clevidipine

Preclinical Development for Clevidipine Name: Institution: Pharmacokinetics & Toxicity Hypertension also referred to as high blood pressure is one of the leading causes of death in the world. The sudden surge of blood pressure damages organs such as the heart. According to the World Health Organization (WHO), hypertension is the second leading cause of fatalities in the world after Cancer. In the U.S, the chronic illness affects over 72 million people who are over 20 years of age. Clevidipine is a U.S drug used in the reduction of blood pressure in patients. The drug is highly effective in controlling acute cases of elevated blood pressure as compared to nitroglycerin and sodium nitroprusside as far as perioperative setting is concerned. Clevidipine is also very effective in patients suffering from acute hypertension. In fact, data shows that the drug is recommended for patients who can only ingest medication intravenously. This characteristic makes the clevidipine the recommended option for patients with hypertensive emergency cases and those undergoing cardiac surgery. This part of the essay shall delve into the use of clevidipine in animals and tissues as part of the pre-clinical development. In pre-clinical developments, major studies were conducted on rats and dogs, as well as limited studies on rabbits. These species aided scientists in making observations on pharmacology, toxicity, metabolism and reproduction studies. The studies involved IV infusion of clevidipine at H152/81 levels in the blood arteries, and the following deductions made. Firstly, clevidipine has linear pharmacokinetics with a short half-life in all species used in the study. It reaches Css levels within 2-5 minutes from the time it is administered intravenously. Finally, clevidipine has the same pharmacokinetics in both male and female species. The blood clearance rates in rabbits, rats and dogs were significantly higher than blood rates, which show that clevidipine has a high hepatic clearance. In addition, the female rats showed a longer half- life for clevidipine due to their significantly lower metabolism as compared to their male counterparts. Repeat doses also increased the rate of clevidipine absorption in dogs. For dogs dosed 12 hours in a day at 50 nmol/kg/min, the hydrolysis of the drug increased to 1.35 minutes from 0.73 between day 1 and 28. The studies revealed that clevidipine had a 99% binding to plasma in all species. The volume of distribution in rats stood at 0.45L while that of rabbits was at 0.17L/kg and 2L/kg in dogs. However, after the administration of the drug, there were high levels of radioactivity experienced in the species within 5 minutes. These were experienced in the blood, the lungs, myocardium, adrenal medulla, the cortex, the tongue, diaphragm, brown fat and the dental pulp. Between 4-16 hours after administering the dosage, H levels in tissues was at a decline. Unusually high levels were evident in urine and the intestines. Some...