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The Role Of Pharmacokinetic Studies In Development Of Drugs, Containing Endogenous Compounds | 8229
ISSN: 0975-0851

Journal of Bioequivalence & Bioavailability
Open Access

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The role of pharmacokinetic studies in development of drugs, containing endogenous compounds

2nd World Congress on Bioavailability & Bioequivalence: Pharmaceutical R & D Summit-2011 and International Conference on Pharmaceutics & Novel Drug Delivery Systems

Oleg Medvedev, Elena Kalenikova, Eugenia Gorodetskaya, Alexander Ivanov, Ekaterina Charitonova

ScientificTracks Abstracts: JBB

DOI: 10.4172/2153-2435.10000S4

Abstract
F inal phase of preclinical development of the new drug includes pharmacokinetic and pharmacodynamic studies in laboratory animals. Th ere are additional requirements for the endogenous molecules, developed as new drug. Pharmakokinetic studies should pay attention on the endogenous level of the compound during the whole duration of blood sampling period. It is important to know the infl uence of pathological process on the endogenous levels of compound in plasma and in the target organ and to correlate its pharmacological eff ect with the aount of compound delivered to the target organ. To provide the optimal transport of endogenous compound to the target organ it is necessary to determine the optimal dose, formulation, route and time schedule of its administration. Th e aim of our study was preclinical study of coenzyme Q10, as cardioprotective agent. Methods: In experiments on male Wistar rats we used ligation of the left coronary a. for modeling acute and chronic regional cardiac ischemia. Levels of CoQ10 in plasma and myocardium were measured by HPLC with electrochemical detection in normal rats and in rats with myocardial ischemia. It was shown, that zone of postischemic necrosis of myocardium and the tissue level of CoQ10 are inversely correlated. Pharmakokinetics of Coq10, administered per os (tablets), intramuscularly (im) and intravenously (iv) (soblubilised form of CoQ10) were studied. Results: It was shown that administration of Q10 via diff erent routes could increase its level in the myocardium, but aft er diff erent delay time. Th e fastest increase by 20% was observed in 30 min aft er iv administration. In the following experiments solution of solubilised form of CoQ10 (Kudesan -?Akvion? Company, Moscow, Russia) was used. Daily administration of CoQ10 (10 mg/kg/day) (3 weeks before the coronary a. occlusion and 3 weeks aft er) was followed by increase in its level in myocardium by 17%, decrease in necrosis zone by 40% and decrease in left ventricle (LV) hypertrophy from 2,38 g/kg (control group) to 2,18 g/kg (CoQ10 treated group). Single iv administration of CoQ10 aft er occlusion of coronary a. was followed by decrease in LV hypertrophy from 2,17 to 2,03 g/kg. In Q10-treated rats development of postinfact LV aneurism and hypertrophy of the right ventricle. Levels of CoQ10 in plasma and myocardium were increased by 87 and 23%. Single iv administration of Coq10 during ischemic period but before the reperfusion, decreased the infarct zone by 30% and diminished the occurrence of reperfusion arrhythmias. In conclusion: Th e results of our study confi rmed the pathogenetic role of CoQ10 defi cite in ischemia-reperfusion conditions and proved the positive eff ect of replenishment of its myocardial tissue levels. Such data may serve as the prove of necessity to develop iv form of CoQ10 containing cardioprotective drug
Biography
Oleg Medvedev has completed his PhD at the age of 26 years from the !st Medical Institute in Leningrad and postdoctoral studies from the Institute of Pharmacology, Moscow. He is the Chairman of the Department of Pharmacology at the Lomonosov Moscow State University. He published more than 200 papers in reputed journals
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