Therapy adherence in elderly of Northern Portugal Poster Presentations August 2015 e99 Background: In patients with type 2 diabetes (T2DM) fixed-dose antihyperglycaemic combinations (FDCs) may provide complemen- tary efficacy, reduce tablet burden, and improve compliance. The aim of this study was to assess the bioequivalence and tolerability of 2 strengths of dapagliflozin (DAPA)/metformin extended-release (MET-XR) FDCs versus their individual components (ICs) in healthy subjects. Material and Methods: This open-label, randomised, 2-way crosso- ver, 4-arm study was conducted in 141 healthy adult Brazilian sub- jects. Two oral doses (5 mg DAPA/500 mg MET-XR and 10 mg DAPA/1000 mg MET-XR) were evaluated in fed and fasted states. Results: Under fed and fasting conditions the 5 mg DAPA/500 mg MET-XR FDC was bioequivalent to its ICs (Table). The 10 mg DAPA/1000 mg MET-XR FDC was bioequivalent to its ICs only in fed patients. C max for metformin was not bioequivalent to its ICs (upper 95% CI outside 80%–125%) in fasted patients; this small increase was not considered clinically meaningful as metformin is recommended to be administered with food. The safety and toler- ability of the FDCs were generally similar to their ICs; no serious adverse events were reported. Conclusions: Both DAPA/MET-XR FDCs were bioequivalent to their ICs, except 10mg DAPA/1000mg MET-XR in fasted patients, sup- porting their use in patients with T2DM. Parameter Geometric mean point estimate of FDC/IC (%) CI (90%) for the point estimate 5 mg DAPA/500 mg MET-XR Arm-1 (n = 34) asted Dapagliflozin C max 104.7 (96.3; 113.7) AUC 0-inf 101.1 (98.0; 104.2) Metformin C max 96.7 (87.1; 107.5) AUC 0-inf 101.7 (93.3; 110.8) Arm-2 (n = 29) Fed Dapagliflozin C max 96.6 (88.0; 106.0) AUC 0-inf 102.0 (98.9; 105.2) Metformin C max 100.9 (95.1; 107.0) AUC 0-inf 104.6 (97.3; 112.4) 10 mg DAPA/1000 mg MET-XR Arm-3 (n = 34) Fasted Dapagliflozin C max 103.7 (96.2; 111.7) AUC 0-inf 102.7 (100.7; 104.8) Metformin C max 118.3 (109.8; 127.5) AUC 0-inf 112.6 (104.8; 120.9) Arm-4 (n = 32) Fed Dapagliflozin C max 91.9 (80.9; 104.4) AUC 0-inf 99.1 (97.0; 101.3) Metformin C max 107.1 (102.6; 111.8) AUC 0-inf 98.6 (93.2; 104.3) 3D PhoToGRAPhy FoR SkIn lESIon QuAnTIFICATIon G. Hogendoorn1; C. Lemoine1,2; R. Rissmann1,2; and J. Burggraaf1,2 1Centre for Human Drug Research, Leiden, The Netherlands; and 2Leiden University, Leiden, The Netherlands Introduction: Reliable methods to quantify skin lesions are critical for the evaluation of disease severity and assessment of therapeu- tic response. In dermatological trials often two dimensional digi- tal photography is utilized which has inherent disadvantages. It appears that high-resolution three-dimensional (3D) imaging may offer many advantages such as offline 3D visualization and auto- matic picture segmentation resulting in an objective and detailed skin lesion characterization. At present this technique is not opti- mally technical and analytical validated which is a pre-requisite for clinical application. Material and Methods: In this study we investigated the perfor- mance and clinical use of the 3D skin-imaging LifeViz™ system (Quantificare, Sophia Antipolis, France) in conjunction with the DermaPix Software. The validation of the LifeViz Micro was con- ducted with four trained operators that captured a synthetic phantom object on three different skin backgrounds at four time points during a period of one week. Results: Coefficient of variations for volume of the 3D system were 1.0%, 2.6% and 1.4% for inter-operator, skin background and inter- day variability, respectively. The overall precision of the system was 2.7% for volume, 1.6% for diameter and 4.1% for height. In order to determine accuracy of the system, a ruler was photographed and a mean error of 0.3% (range 0.0-0.8%) was observed. Preliminary data on cutaneous lesions also show low inter-observer variability and accurate images. Conclusions: This validation study demonstrates that this novel 3D-imaging system is precise and objectively quantifies a phantom object representing a skin lesion. The results support clinical use of this technology enabling high-resolution computation. Also the accu- racy results are promising, but needs to be extended with accuracy assessment of absolute measurements. The preliminary clinical data suggest that application of this non-invasive imaging technique is suitable to quantitatively measure characteristics of cutaneous lesions and may be a promising tool in clinical trials. ThERAPy ADhEREnCE In ElDERly oF noRThERn PoRTuGAl I.C. Pinto1,3; F. Pereira2; and R. Mateos-Campos3,4 1Center for Research and Intervention in the Elderly, Health School of Polytechnic Institute of Bragança, Portugal (isabel. pinto@ipb.pt); 2Center for Research and Intervention in the Elderly, Polytechnic Institute of Bragança, Portugal (fpereira@ ipb.pt); 3School of Pharmacy, University of Salamanca, Spain; and 4INESPO - Innovation Network Spain-Portugal (rmateos@usal.es) Introduction: The elderly population has been growing significantly, leading to an increased prevalence of chronic diseases and conse- quent taking medication. The complex therapies of elderly can lead to therapy non-adherence, increasing several health risks. Aim: This study aimed to estimate the prevalence of therapy adher- ence and associated factors. Material and Methods: This cross-sectional study was based on a questionnaire, with MAT scale (measure of adherence to therapy) validated for the Portuguese population (Lima, 2001) based on the Morisky scale, applied to 52 elderly (≥ 65 years) from northern Portugal. To assess therapy adherence, those whose average adher- ence levels were ≥ 5, were called adherent. It was used descriptive statistics. The level of association between categories of variables was studied through the adjusted residuals (AdR) and the relationship between adherence to the therapeutic and the number of medications taken per day was studied using the Mann-Whitney U test, with a sig- nificance level of 5%. The study was approved by Ethics Committee. Results: The sample consisted mainly of males elderly (61.5% vs. 38.5%), aged between 67 and 98 years (mean 82.71), and while 48.1% was between 75–84 years old. The participants shows high therapy adherence (96.2%). The non-adherent elderly are related to self-med- ication (AdR= 4.3), with the high level of cholesterol (AdR= 2.9) and chronic pain (AdR= 2.9). The non-adherent elderly seem tend to take more drugs per day, although not statistically significant (P = 0.063). Conclusions: This study shows that a large prevalence of elderly adhered to the therapy prescribed. Self-medication, having high cholesterol and chronic pain and higher number of different drugs per day seem related to non-adherence. Key words: Elderly, Therapy adherence, Therapy non-adherence. Clinical Therapeutics e100 Volume 37 number 8S A lIMITED nuMbER oF PRESCRIbED DRuGS ACCounT FoR ThE MAjoRITy oF ClInICAlly RElEVAnT DRuG InTERACTIonS J. Holm1,2; B. Eiermann1; E. Eliasson1,2; and B. Mannheimer1,3 1Karolinska Institutet, Stockholm, Sweden; 2Karolinska University Hospital, Stockholm, Sweden; and 3Södersjukhuset, Stockholm, Sweden Introduction: Drug-drug interactions constitute a predictable and in many cases avoidable cause of adverse drug reactions and thera- peutic failure. We conducted a register-based study to investigate the prevalence of prescribed combinations of interacting drugs in the whole Swedish population (Holm et al. Eur J Clin Pharmacol. 2014). Material and Methods: A retrospective, cross-sectional register study was conducted, covering four months in 2010. Data from the Prescribed Drug Register on all dispensed drug prescriptions in Swedish pharmacies from January 1 to April 30 were linked to the drug-drug interaction database SFINX. The analysis focused on drug interactions classified in the database as clinically relevant that can be handled, e.g. by dose adjustments (C-interactions), and clinically rele- vant interactions that should be avoided (D-interactions). Interactions were categorized according to clinical consequence and drug type and prevalences of interacting drug combinations were described. The study was approved by the Regional Ethics Committee. Results: About half of the population were dispensed at least one drug prescription. Mean (SD) number of dispensed drugs was 3.8 (3.4). About 2.5 million potentially interacting drug combinations were identified in the study population of 9.3 million people. Among detected interactions 38% were classified as C-interactions and 3.8% as D-interactions. About half of all C- and D-interactions were com- binations of drugs with potential to cause therapeutic failure. The 15 most prevalent combinations accounted for 80% of D-interactions. The 10 most prevalent individual drugs were involved in 94% of all D-interactions. Conclusions: A limited number of drugs and a few specific drug combinations account for the majority of D-interactions, i.e. clini- cally relevant interactions that should be avoided, in Sweden. About half of interacting drug combinations among C- and D-interactions potentially leads to treatment failure. ChARACTERIzATIon oF uRACIl CATAbolISM VARIAbIlITy In hEAlThy VolunTEERS D. Kummer1,2; B. Rindlisbacher1; S. Fontana3; J. Sistonen1; U. Amstutz1; and C. Largiadèr1 1Institute of Clinical Chemistry, Bern University Hospital, and University of Bern, Bern, Switzerland; 2Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland; and 3Regional Blood Transfusion Service of the Swiss Red Cross, Bern, Switzerland Uracil catabolism is crucial for the pharmacokinetics of the chemo- therapeutic 5-fluorouracil (5-FU) since 5-FU is degraded by the same pathway. Decreased activity of the first catabolizing enzyme, dihydropyrimidine dehydrogenase (DPD), is a major predictor of 5-FU toxicity with known risk variants in the DPD gene (DPYD) accounting for ~30% of toxicities. However, not all toxicity cases can be explained by DPYD risk variants. To date, the phenotypic variability in the catabolism downstream of DPD by dihydro- pyrimidinase (DHP) and β -ureidopropionase (bUP), potentially contributing to 5-FU toxicity, has not been investigated. Thus, we aimed to characterize the baseline phenotypic variability of endog- enous metabolites and metabolic ratios of 5-FU catabolism enzymes and to correlate the phenotype with genetic variation in the DHP and bUP genes (DPYS and UPB1). Material and Methods: Three variants in DPYS and UPB1 previ- ously associated with 5-FU toxicity were genotyped in 320 healthy volunteers and their plasma uracil, dihydrouracil (UH 2 ), β -ureidopro- pionic acid (UPA), and β -alanine (BAL) concentrations were deter- mined by LC-MS/MS. Results and Conclusions: High inter-individual variability in all met- abolic ratios was observed. Sex-dependent differences were detected at each enzymatic step in the uracil catabolism pathway, with lower metabolite levels (P ≤ 0.007) in women. Moreover, lower UPA/UH 2 ratios (P < 0.001) were observed in women, suggesting that reduced 5-Fluoro-UH 2 catabolism may contribute to higher fluoropyrimi- dine toxicity rates observed in females. Furthermore, volunteers carrying DPYS variant c.265-58T> C had lower UH 2 plasma levels (P = 0.033) and higher UPA/UH 2 ratios (P = 0.036) and carriers of the UPB1 variant c.1-80C> G showed lower BAL plasma levels (P = 0.004). These initial results are in agreement with the previously observed reduced fluoropyrimidine toxicity in c.265-58C carriers and increased toxicity in carriers of c.1-80G, indicating a possible functional effect related to these variants. PolyPhARMACy AnD PoTEnTIAlly InAPPRoPRIATE MEDICATIon In ElDERly oF noRThERn PoRTuGAl I.C. Pinto1,3; F. Pereira2; and R. Mateos-Campos3,4 1Center for Research and Intervention in the Elderly, Health School of Polytechnic Institute of Bragança, Portugal (isabel. pinto@ipb.pt); 2Center for Research and Intervention in the Elderly, Polytechnic Institute of Bragança, Portugal (fpereira@ ipb.pt); 3School of Pharmacy, University of Salamanca, Spain; and 4INESPO - Innovation Network Spain-Portugal (rmateos@usal.es) Introduction: The growing aging of population and increasing preva- lence of chronic diseases require the simultaneous use of drugs, lead to the issue of polypharmacy and potentially interactions and inap- propriate use. Aim: To characterize polymedicated elderly and related factors, iden- tify potentially interactions and inappropriate medication in elderly. Material and Methods: This cross-sectional study was based on a questionnaire applied to 69 elderly (≥ 65 years) from northern Portugal. It was considered as polymedicated seniors taking ≥ 5 drugs. Beers list and the Delafuente classification were used to evalu- ate the therapeutic and possible interactions. It was used descriptive statistics and a model of binary regression, with a significance of 5%. The study was approved by Ethics Committee. Results: The sample consisted mainly of males (53.6% vs. 46.4%), aged between 66 and 99 years (mean 82.01), while 65.2% have more than 80 years. However, most elderly are not polymedicated (58%), on average 4.61 different drugs are administered per day (maximum= 19), antihypertensives (36.2%) and antacids (30.04%) are the most prescribed. Hypertension and depression increase the risk of polymedication eightfold (P = 0.004) and fivefold (P = 0.011) respectively. Female gender seems increase the risk of polypharmacy threefold, although not statistically significant (P = 0.102), and regarding age, the older age group (> 85 years) seems reduces the risk of polypharmacy in 0.6 fold, but also not statistically significant. According with Delafuente classification, 1.4% of elderly has poten- tially drug interactions (Omeprazole and Iron salts). According to the list of Beers, 5.8% of seniors take drugs that classified as having some indications (hydroxyzine, amitriptyline). Conclusions: Regarding polypharmacy, 42% of elderly are poly- medicated with an average of about 5 different drugs per day, anti- hypertensives and antacids the most prescribed. Hypertension and depression are highly associated with polypharmacy. We identified