Cytochrome P450 Oxidoreductase Contribution On An Acenocoumarol Dosing Algorithm

Poster Presentations Sant Pau, Barcelona, Spain; 3Universitat Autònoma de Barcelona, Barcelona, Spain; 4IDIAP Jordi Gol, Barcelona, Spain; and 5SAP Barcelonès Nord i Maresme, Institut Català de la Salut, Barcelona, Spain Background or Introduction:  Generic Drugs Products (GDP) have been subject of discussion for many years, and still now there is some controversy about their quality, effectiveness and safety compared to Innovators drugs. This survey tried to find what is the general perception and opinion from physicians and medical students about generic drugs products. Material and Methods:  A questionnaire of 12 items focused mainly in effectiveness, safety, quality and adverse event occurrence was sent to physicians of a third level health care hospital and to medicine students. Individual demographic information and clinical practice data (specialty, years of experience, pharmaceutical sale representative visits, etc.) was asked. Results:  One hundred fifty-five subjects answered the survey (n =  157). Physicians from specialties that are less related with clinical practice (who do not prescribe daily) showed to be more agreed with the affirmation that Innovators and GDP products have the same quality, effectiveness and adverse event occurrence compare with physician’s that prescribe daily. Internal medicine specialist tends to be more agreed with equivalence in term of effectiveness and adverse events occurrence than surgical specialist. Years of experience, number of patients by day and number of pharmaceutical sales representative’s visits by month showed an inversely proportional relationship to be in agreement with equivalence in quality, effectiveness and safety. Difference between medicine students and physician were found in questions related to quality, effectiveness and safety, physicians tend to be more in disagreement with the equivalence in those aspects between GDP and Innovators ones. All commented results were statistically significant (P values < 0.05). Conclusions:  We found that physicians have some concerns about equivalence between GDP and Innovators ones regarding the quality, efficacy and safety of generic drugs, this concerns increase with years’ experience, number of patients visited and number of sales representatives visits, the fact of prescribing daily and to be surgical specialist. Students tend to be more agreed with equivalence between GDP and Innovators drugs. Nevertheless the response rate is a limitation of this study.

Cytochrome P450 Oxidoreductase Contribution On An Acenocoumarol Dosing Algorithm H.Y. Tong1; A.M. Borobia1,2; R. Lubomirov2; R. Hernández1; M. Muñoz1; E. Ramírez1,2; J. Frías1,2; and A.J. Carcas1,2 1 Clinical Pharmacology Department, Hospital La Paz-Carlos III, IdiPAZ, Madrid, Spain; and 2Pharmacology and Therapeutics Department, School of Medicina, Universidad Autónoma de Madrid, Spain Background:  The great majority of clinically used drugs are metabolized by hepatic type II cytocrome P450 enzymes and require the activity of P450 oxidoreductase (POR). The presence of POR polymorphism can modify the activity of CYP450. Studies about POR influence on the stable dose of warfarin are not conclusive while; there are no studies about its influence on acenocoumarol dosing. Material and Methods:  This was an observational, prospective study. We recruited 341 patients in La Paz University Hospital between 2008 and 2013 in stable anticoagulant treatment with acenocoumarol for atrial fibrillation, thromboembolic disease and valve replacement. Data collection included age, gender, race, body weight and height, INR results and acenocoumarol dose administered in the

August 2015

last 3 months and concomitant medications. A blood sample was prospectively collected for CYP2C9, VKORC1, CYP4F2, APOE and 2 variant of POR [rs2868177 and rs1057868 (POR*28)]. Multiple linear regression was performed to determine the influence of POR SNPs on the acenocoumarol dosing algorithm previously developed by our group. Results:  The real dose of acenocumarol did not differed significantly among carriers of the different polymorphisms of the two POR variants evaluated (POR*28, P =  0.176) and (POR rs2868177, P =  0.534). In the simple regression analysis, none of the POR SNPs was identified as being significantly associated with acenocoumarol dose variation. In the multiple regression analysis, R2 obtained with the acenocoumarol dosing algorithm was 48.5%; adding POR*28 or POR rs2868177 just increase R2 in 0.1%. Conclusions:  None of the 2 POR variants evaluated are associated with the interindividual variability of acenocoumarol.

Manifestations of Unethical Marketing In Health Care of The Kyrgyz Republic A.A. Karasheva1; and U.M. Tilekeeva2 Department of Drug Provision and Medical Equipment Ministry of Health, Bishkek, Kyrgyzstan; and 2Kyrgyz State Medical Academy, Bishkek, Kyrgyzstan Unethical marketing of drug is hot topic around the world. It is necessary to study the actual practice, the implementation of technical regulations. Objective:  Identification of unethical marketing of medicines among 29 clinics in Kyrgyzstan. There were seized 412 forms of an unknown sample, self-pads with advertising for drug prescribing, pharmacy network, engaged in unethical marketing during the checking of 94 doctors. The lists of patients indicated name, phone, address, sheets rewards prizes and bonuses for prescription drugs. Doctors for prescription drugs were provided with bonuses in monetary terms from 10% to 26% of the cost of prescribed drug, household and office equipment, cookware sets, 5% discount cards, vouchers for petroleum products, mobile communications, and trips to luxury resorts. During one month 6 pharmaceutical companies have been presented one workshop, at one of the institutions for the promotion of 6 drugs. In violation of the technical regulations medical representatives visit doctors during medical reception, distribute handouts, prescription forms unknown sample, loose-leaf notebooks with advertising of medicines, conduct workshops without the consent of Department of Drug Provision and Medical Equipment Ministry of Health. Managers and medical representatives of pharmaceutical companies have received official letters on these violations of the ethical principles of promotion of drugs directed newsletters. To reduce the harm of unethical marketing of drugs in Kyrgyzstan it is very important to regulating the monitoring of medical institutions. Repeated violations, by law, must revoke licenses for pharmaceutical activity and registration certificates for drugs. To improve the situation we need to restore the system of professional information about drug and of keeping the medical staff. 1

An Internal System for Quality Assure With External Audit (Aenor) In A Clinical Pharmacology Service: A Positive Experience M. García Sáiz1; E.J. Sanz Álvarez1,2; M. Cervino Rodriguez1; C. Rodríguez Jiménez1; A. Aldea Perona1; and C. Boada Fernández del Campo1

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