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e142 Volume 37 Number 8S aspects of development of topical treatments for AD were not specifically addressed. Conclusions: There is little information available to guide the development of topical dermatological products for the treatment of AD and psoriasis. Because recommendations are disperse, and lacking for some development aspects, a systematic approach to create specific guidance to development in AD and P may be useful.

2013 e83 PP208—Deoxycholic AciD As A MoDifier of the BlooD BrAin BArrier PerMeAtion in rAt M. Lalic-Popovic; S. Golocorbin-Kon; V. Vasovic; B. Milijasevic; and M. Mikov Department of Pharmacy, Faculty of Medicine, Novi Sad, Serbia; Faculty of Pharmacy, University of Montenegro, Podgorica, Montenegro; and Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, Novi Sad, Serbia Introduction: Major problem for diabetic patients represents damage of blood vessels and the oxidative stress of the brain cells due to increased concentration of free radicals and poor nutrition of brain cells. Gliclazide has antioxidative properties and poor blood brain barrier (BBB) penetration. Bile acids are known for their hypoglycemic effect and as prooters of drug penetration across biological membranes. Aim: The aim of this study is to investigate whether the bile acid (deoxycholic acid) can change the permeation of gliclazide, through the blood brain barrier of a rat model type-1 diabetes. Patients (or Materials) and Methods: Twenty-four male Wistar rats were randomly allocated to 4 groups, of which 2 were given alloxan intraperitoneally (100 mg/kg) to induce diabetes. One diabetic group and 1 healthy group were given a bolus gliclazide intra-arterially (20 mg/kg), while the other 2 groups apart from gliclazide got deoxycholic acid (4 mg/kg) subcutaneously. Blood samples were collected 30, 60, 150, and 240 seconds after dose, brain tissues were immediately excised, and blood glucose and gliclazide concentrations were measured. Results: Penetration of gliclazide in groups without deoxycholic acid pretreatment was increased in diabetic animals compared with healthy animals. Also in both, healthy and diabetic animals, deoxycholic acid increased the permeation of gliclazide through that in BBB. Deoxycholic acid pretreatment also changed the pattern of blood glucose level increase after gliclazide application in diabetic as well as in healthy animals. Conclusion: Deoxycholic acid promotes gliclazide penetration across BBB in diabetic and in healthy animals. In addition, deoxycholic acid alters some pharmacokinetic properties of gliclazide in both healthy and diabetic rats. Thus, deoxycholic acid should be more investigated in the treatment of diabetes mellitus and as permeation promoter of lipophilic molecules through BBB as well as other biological membranes. Financial Source: This work has been supported by Ministry of Science and Technology development of Serbia N041012.

2013 e85 Department of Pharmacy, Faculty of Medicine, Novi Sad, Serbia; Faculty of Pharmacy, University of Montenegro, Podogrica, Montenegro; Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, Novi Sad, Serbia; and Faculty of Pharmacy, University of Montenegro, Podogrica, Montenegro Introduction: There are several generic formulations of lamotrigine in Serbia that are widely used in the treatment of patients with epilepsy. The reduction of medical costs with use of generic formulations has potential risk because of the nature of disease, and it is necessary to investigate bioequivalence of each of generic formulations. Aim: Comparison of the efficacy of the reference and generic formulation of lamotrigine and theinvestigation of lamotrigine serum concentrations variation. Date were compared with in vitro results of dissolution profiles of the reference and generic tablet formulation. Patients (or Materials) and Methods: Lamotrigine steady-state concentrations were determined by high-performance liquid chromatography. In clinical study 16 patients participated, of whom 9 received reference formulation and 7 patients received generic formulation. Dissolution characteristics were evaluated at 3 points at physiologic pH range (pH 1.2, pH 4.5, pH 6.8), and difference (f1) and similarity (f2) tests were applied to dissolution data. Results: The relationship between lamotrigine serum concentration (μg/mL) and lamotrigine dose (mg/kg/d) were linear in both formulations (r = 0.78484 original and r = 0.83417 generic). There are statistically significant lower lamotrigine serum concentrations in patient treated with original formulation (3.97 [4.1] μg/mL) than those in patients treated with generic formulations (5.78 [2.7] μg/ mL). No dose-dependent adverse effects appeared in the patients, though patients treated with generic drug were receiving higher doses due to assumption that they are less potent. Brand drug had a lower standard deviation (SD) and data scattering because, as the dissolution data showed, it is less influenced by pH changes. Further dissolution profiles of 2 formulations were only similar in pH 1.2 medium. Conclusion: Investigation showed equal efficacy of 2 lamotrigine formulations, and the variations in plasma concentrations are probably due to individual characteristics of patients and differences in liberation rate of drugs in 2 formulations. It can be claimed that even if there are differences in dissolution profiles of 2 drugs they can have equal therapeutic efficacy. Financial Source: This work has been supported by Ministry of Science and Technology development of Serbia N041012.

PP217—CORRELATION BETWEEN IN VITRO TESTS FOR BLOOD BRAIN BARRIER PENETRATION WITH IN VIVO GLICLAZIDE PENETRATION M. Lalic-Popovic; V. Vasovic; H. Al-Salami; S. Golocorbin-Kon; B. Milijasevic; and M. Mikov Department of Pharmacy; Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, Novi Sad, Serbia; School of Pharmacy, Curtin University, Perth, WA, Australia; and Faculty of Pharmacy, University of Montenegro, Podgorica, Montenegro Introduction: Nowdays, great effort is put into development of effective in vitro model for prediction of blood brain barrier (BBB) penetration of drugs. Recent investigation showed that gliclazide has protective effect on the brain of diabetic rat, but it has low BBB permeability that could be increased. Aim: The aim of this study was to investigate whether in vitro models of gliclazide distribution in systems n-octanol/water and cyclohexane/ water are good in vitro models for the prediction of its penetration as well as for the prediction of influence of dexycholic acid (DCA) influence on penetration. Patients (or Materials) and Methods: Distribution coefficient (logD) was determined using a ...Flask shake “method. Partition profile was determined over physiological pH range (from pH 1.2 HCl solution, pH 4.5 acetate buffer, pH 6.8 and 7.4 phosphate buffer, and pH 7 distilled water) for 5 combinations of n-octanol or cyclohexane with aquase gliclazide solution (10 μg/mL) of different pH and with or without the addition of DCA (0.5 mM) into n-octanol or cyclohexane phase. The analyses were done in triplicate for each pair of organic solvent/ water. Concentrations of gliclazide were determined using high-performance liquid chromatography. Values of logD at pH 7.4 were compared with literature date of gliclazide BBB penetration and influence of DCA on it penetration. Results: Higher partition into organic layer was found in system n-octanol/water than cyclohexane/water. Also DCA increased partition of gliclazide in system cyclohexane/water but not in system n-octanol/ water. Value of logD at pH 7.4 without DCA in organic layer in system n-octanol/water was 0.34 (0.05) and in system cyclohexane/water was –0.74 (0.11). Value of logD at pH 7.4 with DCA in organic layer in system n-octanol/water was 0.54 (0.07) and in system cyclohexane/water was 0.18 (0.01). Thus, partition of gliclazide in system cyclohexane/water better correlate with in vivo data where penetration of gliclazide was increased with DCA pretreatement, but in diabetic animals, penetration was increased in group with and without DCA pretreatment what this in vitro system could not predict. Conclusion: Investigated system cyclohexane/water predicted poor gliclazide BBB penetration and the influence of DA on gliclazide penetration but system n-octanol/water failed to do so. However, more substances are need to claim that system cyclohexane/water successfully could predict drugs BBB penetration. Funding Source: This work has been supported by Ministry of Science and Technology development of Serbia N041012.