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Chrysanthi Tsika, Pavlina A. Tsoka, Manolis Tzatzarakis, Paschalis Efstathopoulos, Sophia Antimisiaris, Ioannis Charalampopoulos, Achilleas Gravanis, Miltiadis K. Tsilimbaris; Bioavailability And Pharmacokinetics Of A Synthetic DHEA Analog, A Novel Anti-apoptotic Agent, After IP Injection In Normal Rodents. Invest. Ophthalmol. Vis. Sci. 2012;53(14):5393.
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© ARVO (1962-2015); The Authors (2016-present)
To investigate the bioavailability of a synthetic Dehydroepiandrosterone (DHEA) analog, a novel anti-apoptotic agent, after intraperitoneal (IP) administration in normal rodents.
The pharmacokinetics in the blood were evaluated in C57BL/6 mice, after IP injection of the molecule’s solution at concentration C=10mg/ml. The blood was collected from the orbital sinus of 5 animals per time point, at time points 0, 30, 60, 120, 240 and 360mins, 12hrs and 24 hrs. The retinal bioavailability was evaluated after transcardial perfusion with Ringer-Lactate solution for 15 min in 5 Sprague-Dawley rats, 2hrs after IP administration (C=10mg/1ml). The molecule was also administered in 5 Sprague Dawley rats in a cyclodextrin solution of the same concentration. The bioavailability in the retina was also evaluated after 2 hrs. The quantification was performed with HPLC LC/MS.
The molecule follows first order kinetics in the blood (k=0.54, t1/2=1.2hrs), while second order kinetics have been measured in the retina tissue in our previous experiments (ARVO 2011). The mean concentration in the retina after perfusion was found 104ng/ml (SD=50.3). The mean concentration of the cyclodextrin-solution in the retina tissue was 194ng/ml (SD= 61.2).
The blood bioavailability of this DHEA analog proved to follow first order kinetics after IP administration in C57BL/6 mice. The difference in kinetics between blood and retina tissue together with the detection of the substance in the retinal tissue after perfusion provide convincing proof of the presence of the substance in the rat retina after intraperitoneal administration. Identification of the substance in the retina after administration of the cyclodextrin formulation is an encouraging outcome for the development of alternative pharmaceutical forms of this anti-apoptotic agent.
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