- Email: [email protected]
Metformin Relative to Single Components in Healthy Subjects
Clinical Therapeutics Material and Methods: The study was conducted on 8 healthy volunteers, following multiple doses of 120 mg of diltiazem MR once daily. Diltiazem concentration was determined up to 24h by fully validated HPLC method. Compartmental analysis of diltiazem pharmacokinetic was used. The temporal profile of diltiazem was described by a one-compartment, first-elimination model. Pharmacodynamic effects were measured continuously (ECG Holter monitoring) up to 24h after drug administration. Classical HRV analysis in time and frequency domains was conducted and a few components of HRV were estimated (RMS, SDNN, LF, and HF). The goodness of fit to pharmacodynamic model interpretation took place with the help of Akaike Information Criterion (AIC). Standard Emax model parameters (EC50, Emax, E0, ke0) were calculated. Results: Mean value (SD)
Parameter Pharmacokinetics ka[h-1] AUC(0-t)[ng/mL*h] MRT[h] Cmax[ng/mL] tmax[h] kel[h-1]
In-vitro evaluation of DDI with cobicistat and ritonavir using heparg cell line
0.3771 (0.1552) 1268 (604) 5.112 (1.531) 115.9 (48.33) 3.689 (0.556) 0.2082 (0.0495)
Pharmacodynamics
Significance of PK/PD correlation (p value) AIC ke0 [h-1] Emax[ms];[ms2] EC50[ng/mL] E0[ms];[ms2]
RMS
SDNN
LF
HF
0.0275
0.0049
0.0033
ns
53.18 (7.53) 1.83 (2.08) 462.50 (443.21) 2120 (2470) 59.37 (16.40)
59.53 (6.26) 0.7092 (1.110) 97.14 (105.91) 105.60 (201.33) 133.81 (23.57)
109.7 (7.7) 3.45 (4.83) 5101 (5922) 240.61 (501.90) 2850 (941.9)
105.7 (10.7) 1.808 (2.002) 1898 (2742) 136.5 (131.0) 1009 (335)
Time delay between the plasma concentrations of diltiazem and the response with the clockwise hysteresis loop was observed. Conclusions: The good fit for Emax model was established. Biophase distribution model with a tolerance to the effect is the most probable PK/PD relationship in regards to AV effects of diltiazem.
Evaluation of CYP450 and transporters expression and activity in heparg cell line under different conditions F. Storelli; C. Bruggmann; F. Doffey-Lazeyras; C. Samer; J. Desmeules; and Y. Daali University Hospitals of Geneva, Geneva, Switzerland Background: HepaRG cell line is able to differentiate to both hepatocyte-like and biliary-like cells after reaching confluence. Previous works have shown that confluent HepaRG cells start to differentiate when adding 2%DMSO in the culture medium. However, DMSO is well known to induce cell death. Methods: In order to optimize CYP450 activity while decreasing cell apoptosis, we tested different culture conditions for differentiation by varying DMSO concentration from 0 to 2% and by adding growth factors EGF and HGF. CYP activity was assessed using a cocktail approach by LC-MS/MS. Expression of several CYP450, phase II enzymes UGT1A1 and UGT2B7 and various transporters was assessed with Nanostring® technology. Results and Conclusions: Increase of DMSO concentration resulted in similar increase of the differentiated pattern. However, cell viability was significantly decreased when adding DMSO up to 2%. Considering CYP450 activity, DMSO increased significantly the activity of CYP3A4, 2B6 and 1A2. The addition of growth factors EGF and HGF was found to have a negative impact on cell
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differentiation and thus CYP activity, but significantly improved cell viability. There was a good correlation between CYP activity and CYP expression (P < 0.05) except for CYP1A2. In all conditions tested, CYP 2D6 showed a weak activity and expression levels were undetectable. UGT1A1 and UGT2B7 transcripts were found at appreciable levels and were influenced by DMSO concentration, as well as hepatic transporters. Efflux transporters MRP2, MRP3 and MDR1 (P-gp) levels were high, whereas BSEP, BCRP and MRP1 levels were low. The uptake transporter OCT1 was largely expressed and OATP1B1, 2B1, OCT3, OAT2 expression were found in acceptable levels. On the contrary, NTCP and OATP1B3 transcripts were undetectable. Differentiation medium containing 1.5% showed similar viability compared to MIL720 from Biopredic® used as reference, with slightly lower CYP450 activities. This medium was thus chosen for further metabolism experiments on the HepaRG cell line.
F. Storelli; C. Bruggmann; F. Doffey-Lazeyras; C. Samer; J. Desmeules; and Y. Daali University Hospitals of Geneva, Geneva, Switzerland Background: Cobicistat is a new pharmacoenhancer which has recently been approved by the EMEA as a boosting agent for the HIV protease inhibitors atazanavir and darunavir. As opposed to ritonavir, cobicistat does not show any antiviral activity. Also, previous inhibition studies on human hepatic microsomal fractions showed a more specific inhibition of CYP3A4 of cobicistat versus ritonavir and a lack of induction potential on CYP3A4. The aim of this work was to investigate CYP450 inhibition/induction potential of major CYPs by cobicistat and ritonavir in HepaRG. Methods: Low density-seeded confluent HepaRG cells were differentiated with 1.5% DMSO and plated in 24-well plates. At day 12 after plating, CYP activity in the presence/absence of cobicistat and ritonavir (0-50 µM) was assessed using a cocktail approach and IC50 was calculated by linear regression. For induction assay, cobicistat or rifampicin (0-50 µM) was incubated with differentiated HepaRG cells for 72 hours in a specific medium (0.5% DMSO, no FBS). DMSO concentration was decreased to 0.5% 24 hours before addition of the inducers. CYP3A4 activity was assessed by incubation of midazolam 5 µM for 3 hours at 37°C and quantification of 1’-hydroxymidazolam by LC-MS/MS. Results: Cobicistat and ritonavir showed similar inhibition of CYP 3A4 with IC50 of 0.107 µM and 0.105 µM respectively. IC50 values of CYP 2B6, 1A2, 2C19 and 2C9 were lower for cobicistat than for ritonavir, thus suggesting that cobicistat may be a more potent inhibitor of these CYP450 than ritonavir. Considering CYP3A4 induction, cobicistat did not seem to induce CYP 3A4. Rifampicin, which was used as a positive control, showed induction of CYP 3A4 up to 1.6 fold. Conclusions: This work has showed the suitability of the HepaRG cell line to study inhibition drug interactions in vitro. Induction assays however have still to be optimized to reach greater levels of induction.
Bioequivalence of Fixed-Dose Combinations of Dapagliflozin/ Metformin Relative to Single Components in Healthy Subjects D.W. Boulton1; M. Chang1; S.C. Griffen2; C. Kitaura1; S. Lubin1; A. Pollack1; and F. LaCreta1 1 Bristol-Myers Squibb Company, Princeton, NJ, USA; and 2 JDRF, New York, NY, USA
Volume 37 Number 8S
Poster Presentations Background: In patients with type 2 diabetes (T2DM) fixed-dose antihyperglycaemic combinations (FDCs) may provide complementary 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 crossover, 4-arm study was conducted in 141 healthy adult Brazilian subjects. 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. Cmax 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 tolerability 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, supporting their use in patients with T2DM. Geometric mean point estimate of FDC/IC (%)
CI (90%) for the point estimate
Cmax
104.7
(96.3; 113.7)
AUC0-inf Cmax AUC0-inf Cmax
101.1 96.7 101.7 96.6
(98.0; 104.2) (87.1; 107.5) (93.3; 110.8) (88.0; 106.0)
AUC0-inf Cmax AUC0-inf
102.0 100.9 104.6
(98.9; 105.2) (95.1; 107.0) (97.3; 112.4)
Cmax
103.7
(96.2; 111.7)
AUC0-inf Cmax AUC0-inf Cmax
102.7 118.3 112.6 91.9
(100.7; 104.8) (109.8; 127.5) (104.8; 120.9) (80.9; 104.4)
AUC0-inf Cmax AUC0-inf
99.1 107.1 98.6
(97.0; 101.3) (102.6; 111.8) (93.2; 104.3)
Parameter 5 mg DAPA/500 mg MET-XR Arm-1 (n = 34) Dapagliflozin asted Metformin Arm-2 (n = 29) Fed
Dapagliflozin
Metformin 10 mg DAPA/1000 mg MET-XR Arm-3 (n = 34) Dapagliflozin Fasted Metformin Arm-4 (n = 32) Fed
Dapagliflozin
Metformin
3D photography for Skin lesion Quantification G. Hogendoorn1; C. Lemoine1,2; R. Rissmann1,2; and J. Burggraaf1,2 1 Centre for Human Drug Research, Leiden, The Netherlands; and 2 Leiden University, Leiden, The Netherlands Introduction: Reliable methods to quantify skin lesions are critical for the evaluation of disease severity and assessment of therapeutic response. In dermatological trials often two dimensional digital 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 automatic picture segmentation resulting in an objective and detailed skin lesion characterization. At present this technique is not optimally technical and analytical validated which is a pre-requisite for clinical application.
August 2015
Material and Methods: In this study we investigated the performance 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 conducted 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 interday 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 accuracy 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 Center for Research and Intervention in the Elderly, Health School of Polytechnic Institute of Bragança, Portugal (isabel. [email protected]); 2Center for Research and Intervention in the Elderly, Polytechnic Institute of Bragança, Portugal (fpereira@ ipb.pt); 3School of Pharmacy, University of Salamanca, Spain; and 4 INESPO - Innovation Network Spain-Portugal ([email protected]) Introduction: The elderly population has been growing significantly, leading to an increased prevalence of chronic diseases and consequent 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 adherence 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 adherence 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 significance 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-medication (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.
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Parameter Pharmacokinetics ka[h-1] AUC(0-t)[ng/mL*h] MRT[h] Cmax[ng/mL] tmax[h] kel[h-1]
In-vitro evaluation of DDI with cobicistat and ritonavir using heparg cell line
0.3771 (0.1552) 1268 (604) 5.112 (1.531) 115.9 (48.33) 3.689 (0.556) 0.2082 (0.0495)
Pharmacodynamics
Significance of PK/PD correlation (p value) AIC ke0 [h-1] Emax[ms];[ms2] EC50[ng/mL] E0[ms];[ms2]
RMS
SDNN
LF
HF
0.0275
0.0049
0.0033
ns
53.18 (7.53) 1.83 (2.08) 462.50 (443.21) 2120 (2470) 59.37 (16.40)
59.53 (6.26) 0.7092 (1.110) 97.14 (105.91) 105.60 (201.33) 133.81 (23.57)
109.7 (7.7) 3.45 (4.83) 5101 (5922) 240.61 (501.90) 2850 (941.9)
105.7 (10.7) 1.808 (2.002) 1898 (2742) 136.5 (131.0) 1009 (335)
Time delay between the plasma concentrations of diltiazem and the response with the clockwise hysteresis loop was observed. Conclusions: The good fit for Emax model was established. Biophase distribution model with a tolerance to the effect is the most probable PK/PD relationship in regards to AV effects of diltiazem.
Evaluation of CYP450 and transporters expression and activity in heparg cell line under different conditions F. Storelli; C. Bruggmann; F. Doffey-Lazeyras; C. Samer; J. Desmeules; and Y. Daali University Hospitals of Geneva, Geneva, Switzerland Background: HepaRG cell line is able to differentiate to both hepatocyte-like and biliary-like cells after reaching confluence. Previous works have shown that confluent HepaRG cells start to differentiate when adding 2%DMSO in the culture medium. However, DMSO is well known to induce cell death. Methods: In order to optimize CYP450 activity while decreasing cell apoptosis, we tested different culture conditions for differentiation by varying DMSO concentration from 0 to 2% and by adding growth factors EGF and HGF. CYP activity was assessed using a cocktail approach by LC-MS/MS. Expression of several CYP450, phase II enzymes UGT1A1 and UGT2B7 and various transporters was assessed with Nanostring® technology. Results and Conclusions: Increase of DMSO concentration resulted in similar increase of the differentiated pattern. However, cell viability was significantly decreased when adding DMSO up to 2%. Considering CYP450 activity, DMSO increased significantly the activity of CYP3A4, 2B6 and 1A2. The addition of growth factors EGF and HGF was found to have a negative impact on cell
e98
differentiation and thus CYP activity, but significantly improved cell viability. There was a good correlation between CYP activity and CYP expression (P < 0.05) except for CYP1A2. In all conditions tested, CYP 2D6 showed a weak activity and expression levels were undetectable. UGT1A1 and UGT2B7 transcripts were found at appreciable levels and were influenced by DMSO concentration, as well as hepatic transporters. Efflux transporters MRP2, MRP3 and MDR1 (P-gp) levels were high, whereas BSEP, BCRP and MRP1 levels were low. The uptake transporter OCT1 was largely expressed and OATP1B1, 2B1, OCT3, OAT2 expression were found in acceptable levels. On the contrary, NTCP and OATP1B3 transcripts were undetectable. Differentiation medium containing 1.5% showed similar viability compared to MIL720 from Biopredic® used as reference, with slightly lower CYP450 activities. This medium was thus chosen for further metabolism experiments on the HepaRG cell line.
F. Storelli; C. Bruggmann; F. Doffey-Lazeyras; C. Samer; J. Desmeules; and Y. Daali University Hospitals of Geneva, Geneva, Switzerland Background: Cobicistat is a new pharmacoenhancer which has recently been approved by the EMEA as a boosting agent for the HIV protease inhibitors atazanavir and darunavir. As opposed to ritonavir, cobicistat does not show any antiviral activity. Also, previous inhibition studies on human hepatic microsomal fractions showed a more specific inhibition of CYP3A4 of cobicistat versus ritonavir and a lack of induction potential on CYP3A4. The aim of this work was to investigate CYP450 inhibition/induction potential of major CYPs by cobicistat and ritonavir in HepaRG. Methods: Low density-seeded confluent HepaRG cells were differentiated with 1.5% DMSO and plated in 24-well plates. At day 12 after plating, CYP activity in the presence/absence of cobicistat and ritonavir (0-50 µM) was assessed using a cocktail approach and IC50 was calculated by linear regression. For induction assay, cobicistat or rifampicin (0-50 µM) was incubated with differentiated HepaRG cells for 72 hours in a specific medium (0.5% DMSO, no FBS). DMSO concentration was decreased to 0.5% 24 hours before addition of the inducers. CYP3A4 activity was assessed by incubation of midazolam 5 µM for 3 hours at 37°C and quantification of 1’-hydroxymidazolam by LC-MS/MS. Results: Cobicistat and ritonavir showed similar inhibition of CYP 3A4 with IC50 of 0.107 µM and 0.105 µM respectively. IC50 values of CYP 2B6, 1A2, 2C19 and 2C9 were lower for cobicistat than for ritonavir, thus suggesting that cobicistat may be a more potent inhibitor of these CYP450 than ritonavir. Considering CYP3A4 induction, cobicistat did not seem to induce CYP 3A4. Rifampicin, which was used as a positive control, showed induction of CYP 3A4 up to 1.6 fold. Conclusions: This work has showed the suitability of the HepaRG cell line to study inhibition drug interactions in vitro. Induction assays however have still to be optimized to reach greater levels of induction.
Bioequivalence of Fixed-Dose Combinations of Dapagliflozin/ Metformin Relative to Single Components in Healthy Subjects D.W. Boulton1; M. Chang1; S.C. Griffen2; C. Kitaura1; S. Lubin1; A. Pollack1; and F. LaCreta1 1 Bristol-Myers Squibb Company, Princeton, NJ, USA; and 2 JDRF, New York, NY, USA
Volume 37 Number 8S
Poster Presentations Background: In patients with type 2 diabetes (T2DM) fixed-dose antihyperglycaemic combinations (FDCs) may provide complementary 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 crossover, 4-arm study was conducted in 141 healthy adult Brazilian subjects. 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. Cmax 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 tolerability 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, supporting their use in patients with T2DM. Geometric mean point estimate of FDC/IC (%)
CI (90%) for the point estimate
Cmax
104.7
(96.3; 113.7)
AUC0-inf Cmax AUC0-inf Cmax
101.1 96.7 101.7 96.6
(98.0; 104.2) (87.1; 107.5) (93.3; 110.8) (88.0; 106.0)
AUC0-inf Cmax AUC0-inf
102.0 100.9 104.6
(98.9; 105.2) (95.1; 107.0) (97.3; 112.4)
Cmax
103.7
(96.2; 111.7)
AUC0-inf Cmax AUC0-inf Cmax
102.7 118.3 112.6 91.9
(100.7; 104.8) (109.8; 127.5) (104.8; 120.9) (80.9; 104.4)
AUC0-inf Cmax AUC0-inf
99.1 107.1 98.6
(97.0; 101.3) (102.6; 111.8) (93.2; 104.3)
Parameter 5 mg DAPA/500 mg MET-XR Arm-1 (n = 34) Dapagliflozin asted Metformin Arm-2 (n = 29) Fed
Dapagliflozin
Metformin 10 mg DAPA/1000 mg MET-XR Arm-3 (n = 34) Dapagliflozin Fasted Metformin Arm-4 (n = 32) Fed
Dapagliflozin
Metformin
3D photography for Skin lesion Quantification G. Hogendoorn1; C. Lemoine1,2; R. Rissmann1,2; and J. Burggraaf1,2 1 Centre for Human Drug Research, Leiden, The Netherlands; and 2 Leiden University, Leiden, The Netherlands Introduction: Reliable methods to quantify skin lesions are critical for the evaluation of disease severity and assessment of therapeutic response. In dermatological trials often two dimensional digital 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 automatic picture segmentation resulting in an objective and detailed skin lesion characterization. At present this technique is not optimally technical and analytical validated which is a pre-requisite for clinical application.
August 2015
Material and Methods: In this study we investigated the performance 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 conducted 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 interday 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 accuracy 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 Center for Research and Intervention in the Elderly, Health School of Polytechnic Institute of Bragança, Portugal (isabel. [email protected]); 2Center for Research and Intervention in the Elderly, Polytechnic Institute of Bragança, Portugal (fpereira@ ipb.pt); 3School of Pharmacy, University of Salamanca, Spain; and 4 INESPO - Innovation Network Spain-Portugal ([email protected]) Introduction: The elderly population has been growing significantly, leading to an increased prevalence of chronic diseases and consequent 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 adherence 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 adherence 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 significance 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-medication (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.
1
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