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Introduction The aim of our study was to compare the level of the most common organophosphate metabolite, dimethyl phosphate, in urine of women giving birth to both boys with cryptorchidism (study group), and healthy boys (control group), as well as to compare the level of dimethyl phosphate in our population with the results obtained in other populations. Material and methods After the ethical approval we included thirty women in both study and control groups. All newborns were born between 38 and 42weeks' gestation. Urine samples were taken on 3rd postpartal day. Gas chromatography with flame photometric detection was used to analyze dimethyl phosphate in urine following the method of Wu et al. Statistical analysis was done using Mann–Whitney test to compare the results in the two groups. Results Geometric mean of dimethyl phosphate in the study group was 7.18±8.26μg/L and the creatinine-corrected level was 5.63±5.95μg/L, and in the control group, the values are 7.98±6.75μg/L and 6.15±7.01μg/L, respectively. There was not a statistically significant difference in levels of dimethyl phosphate between these two groups ( p =0.72786). Dimethyl phosphate levels obtained in similar studies are: 14.4μg/L in Israel, 3.7μg/L in Palestine, 10.3μg/L in Jerusalem, 1.60μg/L in Caribbean islands and 2.60μg/L in Canada. Conclusions Pregnant women in our country are exposed to organophosphate pesticides, but a correlation between the exposure to organophosphate pesticides and cryptorchidism was not found. Level of evidence I. Type of study : Prognostic study, prospective study.

Binary polymeric amorphous carvedilol solid dispersions were prepared using solvent method by varying solvent type, polymer type and carvedilol to polymer ratio in order to assess the influence of these factors and maximize carvedilol dissolution rate. Low and high molecular weight polyvinylpyrrolidone, polyvinylpyrrolidone-vinyl acetate copolymer and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer were used as polymeric carriers in carvedilol to polymer ratios 1:1, 1:2 or 1:4, while absolute ethanol or acetone were used as solvents. Hard gelatin capsules were prepared with carvedilol solid dispersion and lactose monohydrate, mannitol or microcrystalline cellulose. FTIR and PXRD were used to detect carvedilol crystallinity and identify carvedilol-polymer interactions and carvedilol polymorphs. These techniques confirmed carvedilol transition to amorphous state and suggested that hydrogen bonds were formed between carvedilol and polymer molecules. Carvedilol dissolution rate was significantly higher from solid dispersions with higher carvedilol to polymer ratio and solid dispersions prepared using the solvent in which the polymer was more soluble. Solid dispersion with polyvinylpyrrolidone-vinyl acetate copolymer in 1:4 ratio in absolute ethanol displayed the highest carvedilol dissolution rate with 91.78% carvedilol dissolved in the first 30 min. Capsules prepared with the selected solid dispersion and microcrystalline cellulose as diluent displayed the highest carvedilol dissolution rate, with 93.43% carvedilol dissolved within the first 30 min. Carvedilol bioavailability was significantly increased by formulating solid dispersions, while the analysis of serum biochemical parameters excluded damage on liver and kidney function and the lipid profile of animals exposed to investigated drug delivery system.

Role of BeNzodiazepiNeS iN CaRdiaC SafeTy of low MeThadoNe doSeS iN paTieNTS duRiNg MeThadoNe MaiNTeNaNCe TReaTMeNT S. Petkovic ; V. Mijatovic ; I. Samojlik; S. Vukmirovic ; A. Dickov; and T. Popov Faculty of Medicine, University of Novi Sad, Vojvodina, Serbia; and Institute of Cardiovascular Diseases Vojvodina, Sremska Kamenica, Serbia Introduction: Despite the fact that most of health care professionals are aware of possible respiratory depressant effect of methadone and benzodiazepines coadministration, recently published data reveal that ventricular arrhythmia and cardiac arrest are currently the most frequent adverse event attributed to methadone and benzodiazepine comedication. The aim of this study is to assess cardiac safety of low methadone doses used concomitantely with benzodiazepines in opiate addicts in methadone maintenance treatment (MMT). Material and Methods: A clinical trial in which participated 30 opiate addicts at the start of MMT was performed. ECG (to calculate corrected QT (QTc) interval) and blood sampling (to determine methadone and diazepam concentrations ) were performed in all study participants at 3 time points (before the introduction of MMT, after 1 and 6 mo of MMT). Methadone and diazepam concentrations in serum were determined by using liquid chromatography-mass spectrometry (LC-MS). Results: The length of QTc interval before the introduction of MMT was 411.87 ± 27.22 ms, after 1 month of MMT 425.20 ± 17.71 ms and after 6 months of MMT 423.50 ± 14.72 ms. The mean methadone concentration at observed time points was 176.77 ± 118.56 ng/ mL and 342.86 ± 181.54 ng/mL, respectively, while the mean diazepam concentration was 560.74 ± 436.72 ng/mL and 1045.32 ± 932.72 ng/mL, respectively. There was a statistically significant increase in the length of QTc interval after 1 and 6 months of MMT in comparison to the value before the application of MMT. A statistically significant correlation between the concentration of methadone and QTc interval length after 1 and 6 months of MMT was observed and it remained statistically significant if concentration of diazepam was included. Conclusions: Further studies could clarify the possible role of benzodiazepines in the increasing cardiotoxicity of methadone in opiate addicts in MMT. Acknowledgement: The Ministry of Education and Science of the Republic of Serbia (grant numbered 41012) supported this research work.

e30 Volume 35 Number 8S Conclusion: LHA tends to accept EU requirements as much as it could match local regulation, but local regulation differs significantly from EU. As a consequence, LSU makes additional efforts and communications with LHA and Company, to fulfill each requirement in its own way. The differences could be overcome with harmonization of local regulation with EU and if LHA receive access to EudraVigilance database. Disclosure of Interest: None declared.