Category Archives: Pharmaceutical Science

Brazilian agriculture as source of raw material to organic cosmetics

J Pharm Pharmacogn Res 5(3): 165-166, 2017.

Letter to the Editor | Carta al Editor

The profile of Brazilian agriculture as source of raw material to obtain organic cosmetics

[El perfil de la agricultura brasileña como fuente de materia prima para obtener cosméticos orgánicos]

Neila de Paula Pereira, Douglas Dourado*

Laboratory of Research of Medicines and Cosmetics (LAPEMEC). Federal University of Bahia (UFBA), Salvador, Brazil.

Dear Editor:

The concept of organic products has expanded beyond food sector foods. Althougth it still causes resistance in some people, it has already captured a wide public, since the basic conditions that define organic products are an absence of agricultural toxins and chemical fertilizers during cultivation. True organic cosmetics are composed only of natural ingredients, with a minimum of 95% of the raw materials used, produced according to the precepts of organic agriculture. They also do not contain preservatives, synthetic fragrances, or petroleum derivatives, among other components of non-natural origin (Kapsnet, 2007; Ethos, 2012). This differentiates them in terms of composition from other cosmetics that claim to possess organic ingredients, i.e., among other non-organic raw materials that make up such products, which additionally contain organic ingredients.

Pereira (2009) has stated that the cosmetics represent the greatest investment in research involving natural raw materials, especially in Brazil, which with the exploration of its biodiversity, adopted agroforestry type production processes that integrate vegetation production with the ecosystem, producing environmental, social, and economic benefits. Therefore, a significant element in the spread of organic cosmetics in Brazil is related to policies for sustainability, which promote environmental integrity through the practice of using non-extractive raw materials, as well as recycling packaging. To assure that all the requirements of organic products are met agencies emerged (ECOCERT and IBD) inspect and certify the production from the raw materials stage through to the finished product (Higuchi, 2013). At the beginning of the 1980, the Institute of Biodynamic Development was founded (IBD, 2009). The only 100% nationally regulated institute, internationally recognized, which carries the credentials for exports destined for all countries. In addition, health researchers are concerned about the raw materials used in the manufacture of cosmetics, which cause allergies, proposing therefore, organic cosmetics as an alternative (De Buzin, 2016).

With one of the most notable floras in the world for sustainable research, the Brazilian Amazon region currently counts on financial incentives from the Brazilian Government for private national and foreign businesses. The ongoing implantation of a Biocosmetics Research and Development Network (REDEBIO) aims to stimulate research involving natural resources from the Brazilian states that make up the zone defined as “Amazônia Legal”. The objective of this region, still under development in Brazil, is principally to aggregate value to products manufactured in small local industries through the use of sustainable technology currently being established. Certain certified raw materials already included in the country’s sustainability program, have also begun to be cultivated according to the requirements of organic cultivation (Neves, 2009). The majority are species of Amazonian vegetation: Euterpe oleracea (Açai), Orbignya martiana (Babaçu), Theobroma grandi-florum (Cupuaçu), Carapas guianensis (Andiroba), Pentaclethra macroloba (Pracaxi), Copaifera landesdorffi (Copaiba), Platonia insignis (Bacuri), Theobroma cacao (Cacao), Virola surinamensis (Ucuuba) and Bertholletia excelsa (Brazil nut). These generate phytopreparations, such as oils, extracts, and dyes that are widely used in the manufacture of Brazilian organic cosmetics with scientifically proven topical and capillary benefits (ABIHPEC, 2012). In the final balance, Brazilian organic cosmetics should continue to gain force over the next few years, especially with the regulation of the organic cosmetics market that is being drafted by the Brazilian Ministry of Agriculture. Moreover, lines of ecologically aware products that provide quality of life for both for rural and metropolitan communities show a tendency to occupy greater space in the market.


ABIHPEC (2012) Brazilian Association of the Personal Hygiene, Perfumery and Cosmetics Industry. [Consulted December 10, 2016].

De Buzin EJWK (2016) Mercado de produtos orgânicos em Goiânia: Venda direta. PhD Thesis, Department of Agronomy, Federal University of Goias, Goiânia, Brazil.

Ethos (2012) Institute of Business and Social Responsibility. [Consulted December 5, 2016].

Higuchi CT (2013) The rational use of cosmetics and its disposal and aware of appeal for use products organic and natural sources. InterfacEHS 8(3): 138-142.

IBD (2009) Guidelines for certification of health care products and organic beauty, and natural and organic raw materials and natural. [Consulted December 1, 2016].

Kapsner T (2007) Organic cosmetic standards: A new formulation challenge. Cosmet Toiletries 122: 71‑78.

Neves K (2009) Green formulation. Cosmet Toiletries 21: 22-30.

Pereira NP (2009) Sustainability of cosmetic products in Brazil. J Cosmet Dermatol 8: 160‑161.

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Citation Format: Pereira NP, Dourado D (2017) The profile of Brazilian agriculture as source of raw material to obtain organic cosmetics. J Pharm Pharmacogn Res 5(3): 165-166.

© 2017 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

In vitro studies of glibenclamide microspheres

J Pharm Pharmacogn Res 5(2): 78-87, 2017.

Original Article | Artículo Original

Evaluation of glibenclamide microspheres for sustained release

[Evaluación de microesferas de glibenclamida para liberación sostenida]

Kambham Venkateswarlu*

Department of Pharmaceutics, JNTUA Oil Technological and Pharmaceutical Research Institute, Ananthapuramu, Andhra Pradesh-515001, India.



Context: Sustained release drug delivery systems are more preferred than the conventional drug delivery systems due to its enhanced bioavailability and patient compliance. Earlier studies reported on glibenclamide (GBCM) were not clear and hence, the step has been taken to explore the sustained release drug delivery system of GBCM.

Aims: To evaluate the sustained release microspheres obtained of GBCM.

Methods: Microspheres were prepared by ionic gelation method using the polymers like Eudragit RS 100 and xanthan gum. Polymers can sustain the drug release from microspheres. The prepared microspheres were subjected to micromeritic studies like Carr’s index, Hausner’s ratio and angle of repose.

Results: Micromeritic studies confirmed that the microspheres possessing acceptable flow properties. It was observed from the in vitro release studies, formulations F8 and F9 showed sustained drug release for desired time of 12 h and when compared to F9, formulation F8 showed maximum drug release for 12 h.

Conclusions: Results confirmed the formulation F8 consist of the polymers such as Eudragit RS 100 about 150 mg and xanthan gum about 100 mg showed desired sustained release of 12 h with 96.07% and kinetic studies confirmed that the release from microspheres followed non-Fickian diffusion mechanism. Due to its sustained release property, it could enhance the bioavailability of drug thereby improves the patient compliance and expect better treatment than conventional dosage forms.

Keywords: Eudragit RS 100; glibenclamide; ionic gelation method; sustained release; xanthan gum.



Contexto: Los sistemas de suministro de fármacos de liberación sostenida son más preferidos que los sistemas convencionales de administración debido a su mejor biodisponibilidad y al cumplimiento del paciente. Los estudios anteriores sobre glibenclamida (GBCM) no fueron claros, por lo que se decidió explorar el sistema de liberación sostenida de fármacos de GBCM.

Objetivos: Evaluar las microesferas de acción sostenida obtenidas de GBCM.

Métodos: Las microesferas se prepararon mediante un método de gelificación iónica con polímeros como Eudragit RS 100 y goma xantano. Los polímeros pudieron sostener la liberación del fármaco a partir de microesferas. Las microesferas preparadas se sometieron a estudios micromeríticos como el índice de Carr, la relación de Hausner y el ángulo de reposo.

Resultados: Los estudios microméríticos confirmaron que las microesferas poseen propiedades de flujo aceptables. Se observó, a partir de los estudios de liberación in vitro, que las formulaciones F8 y F9 mostraron una liberación sostenida del fármaco durante un tiempo deseado de 12 horas y cuando se comparó con F9, la formulación F8 mostró liberación máxima del fármaco durante 12 h.

Conclusiones: Los resultados confirmaron que la formulación F8 constituida de polímeros tales como Eudragit RS 100 (150 mg) y goma xantano (100 mg) mostró una liberación sostenida deseada de 12 h con 96,07% y estudios cinéticos confirmaron que la liberación de microesferas seguía mecanismo de difusión no Fickiano. Debido a su propiedad de liberación sostenida, esta podría mejorar la biodisponibilidad del fármaco, por lo tanto, mejorar el cumplimiento del paciente y se esperaría un mejor tratamiento que las formas de dosificación convencionales.

Palabras Clave: Eudragit RS 100; glibenclamida; goma xantano; liberación sostenida; método de gelificación iónica.


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Citation Format: Venkateswarlu K (2017) Evaluation of glibenclamide microspheres for sustained release. J Pharm Pharmacogn Res 5(2): 78-87.
This article has been cited by:
Manyam N, Reddy Budideti KK, Mogili S (2018) Formulation and in-vitro evaluation of nanosponge loaded extended release tablets of trimethoprim. UPI Journal of Pharmaceutical, Medical and Health Sciences 1(1): 78-86. Website
Kambham Venkateswarlu, Manyam Nirosha, Budideti Kishore Kumar Reddy, Badithala Siva Sai Kiran (2017) Effect of directly compressible excipient and treated agar on drug release of clopidogrel oral disintegrating tablets. Therapeutic Delivery 8(8): 615-624. DOI: 10.4155/tde-2017-0019

© 2017 Journal of Pharmacy & Pharmacognosy Research (JPPRes)

Límites de biocontaminación en superficies

J Pharm Pharmacogn Res 4(3): 115-121, 2016.

Short Communication | Comunicación Corta

Determinación de los límites de la contaminación microbiana presente en superficies de un laboratorio de referencia distrital de microbiología farmacéutica

[Limits determination of microbial contamination present on surfaces from a pharmaceutical microbiology district reference laboratory]

Natalia Charry*, Sandra L. Gómez

Laboratorio de Salud Pública. Dirección de Epidemiología, Análisis y Gestión de Políticas en Salud Colectiva. Secretaría Distrital de Salud, Bogotá, Colombia.

Context: The bioburden present on the pharmaceutical microbiology laboratory’s surfaces, may increase the risk of cross-contamination when analytical tests are being carried out; periodic monitoring allows to set limits that reduce the risk.

Aims: To determinate the limits of bioburden present on seven surfaces of the pharmaceutical microbiology laboratory, after the cleaning and disinfection process.

Methods: The swabbing method was used for sampling. With a 25 cm2 stencil and a sterile swab, a sample was taken, passing the swab over five points of every surface chosen. A total aerobic microbial count and a total yeast and mold count was done. Finally, the average and the standard deviation of the counts was obtained.

Results: The average from the counts obtained on each surface selected for the study, were below the recommended limits by international entities like the World Health Organization and the European Union, between others; also, the results generated in this study, allow to classify the biosafety cabinet as an ISO 5 area and the other areas as ISO 7.

Conclusions: Bioburden levels on the tested surfaces are considered low, reducing the risk of cross-contamination, which could have a negative impact on laboratory’s activities. Also, it follows that disinfectant concentration used, is effectively.

Keywords: Controlled environment: cross-contamination; disinfection; surfaces sampling.


Contexto: La presencia de carga microbiana en las superficies de un laboratorio de microbiología farmacéutica, puede aumentar el riesgo de contaminación cruzada durante el desarrollo de las pruebas analíticas; realizar monitoreos periódicos permite establecer límites que disminuyan dicho riesgo.

Objetivos: Determinar los límites de la contaminación microbiana presente en siete superficies del laboratorio de microbiología de medicamentos, después de llevar a cabo el proceso de limpieza y desinfección.

Métodos: Se empleó el método de hisopado para la toma de las muestras. Con la ayuda de un hisopo estéril y una plantilla de 25 cm2, se tomaron muestras en cinco puntos de cada superficie. Se realizó el recuento de microorganismos mesófilos aerobios, mohos y levaduras. Por último, se obtuvo el promedio y desviación estándar de los recuentos.

Resultados: El promedio de los recuentos obtenidos en todas las superficies objeto de estudio, se encontraron por debajo de los límites recomendados por entes internacionales como la Organización Mundial de la Salud y la Unión Europea, entre otras; así mismo, los resultados generados, permiten clasificar la cabina de bioseguridad como un área ISO 5 y las demás áreas como ISO 7.

Conclusiones: Se considera que los niveles de contaminación microbiana presente en las superficies evaluadas son bajos, disminuyendo el riesgo de contaminación cruzada que afecte las actividades propias del área; así mismo, se infiere que la concentración del desinfectante usado es efectiva.

Palabras Clave: Ambiente controlado; contaminación cruzada; desinfección; muestreo de superficies.

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Citation Format: Natalia Charry, Sandra L. Gómez (2016) Determinación de los límites de la contaminación microbiana presente en superficies de un laboratorio de referencia distrital de microbiología farmacéutica. | [Limits determination of microbial contamination present on surfaces from a pharmaceutical microbiology district reference laboratory]. J Pharm Pharmacogn Res 4(3): 115-121.

© 2016 Journal of Pharmacy & Pharmacognosy Research (JPPRes)


J Pharm Pharmacogn Res 3(suppl. 1): S74, 2015

Proceedings of the 4th International Symposium on Pharmacology of Natural Products FAPRONATURA 2015  September 21st-25th, 2015; Cuban Society of Pharmacology. Topes de Collantes, Sancti Spiritus, Cuba.

Oral Communication


Monteserín A1, Pérez Y2, Sánchez A3.

1Faculty of Biology, University of Havana, Cuba, 25th street, #. 455. Vedado, Plaza de la Revolución, Havana, Cuba. E-mail:
2Faculty of Chemistry, University of Havana, Cuba, Zapata e/G y Carlitos Aguirre. Vedado, Plaza de la Revolución, Havana, Cuba.


Introduction: The appearance of chronical degenerative diseases has a close relationship with the DNA damage in somatic cells. The damage can be originated by different genotoxic agents, as for example the aromatic amines. At the present, it is considered as possible way to prevent and treat these affections the use of chemoprotective phythocompounds. It has been studied that the total aqueous extract of the cuban specie Phyllanthus orbicularis Kunth reduce significantly the damage induced by the aromatic amines: m-phenilendiamine (m-PDA), 4-aminobiphenyl (4-ABP) y 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) and from the total aqueous fractioned extract was isolated and identified the 2,6 – disecbutilphenol (DSBP). However, it is not known how the DSBP protects at a molecular level. Thanks’ to the advances in computational chemistry and modelations tools is possible to study the direct chemical interaction between the DSBP and the aromatic amines as possible genoprotective mechanism. Material and Methods: The starting chemical structures of the DSBP and the three amines: m–PDA, 4 – ABP and PhIP were geometrical and electronically optimized. The different association complexes between the phenol and the aromatic amines were generated by Multiple Minimum Hypersurface (MMH) and optimized with the semiempirical methods AM1 and PM6 – d. The association energies for each complex were obtaining with the program Q3. Finally, the more stable complexes were reoptimized at a DFT level using the B3LYP and M052x functional. Results: The results allowed demonstrated that the association between the phenol and the amines was thermodynamically favored and it can be predicted through this research a genoprotective order for the phenol against each amine and which chemical groups of the amine and the phenol interact. Conclusions: This research work allows us to propose the chemical direct interaction between the phenol and the amines as possible molecular mechanism for the DNA protection.

Citation Format: Monteserín A, Pérez Y, Sánchez A (2015) Computational study of the dna protective effect of the 2,6–disecbutilphenol extracted from the plant Phyllanthus orbicularis Kunth. [Abstract]. In: Proceedings of the FAPRONATURA 2015; 2015 Sep 21-25; Topes de Collantes, Sancti Spiritus: CSF. J Pharm Pharmacogn Res 3(Suppl. 1): S74. Abstract nr OC-51.


J Pharm Pharmacogn Res 3(suppl. 1): S94, 2015

Proceedings of the 4th International Symposium on Pharmacology of Natural Products FAPRONATURA 2015  September 21st-25th, 2015; Cuban Society of Pharmacology. Topes de Collantes, Sancti Spiritus, Cuba.



Quiñonez-Bastidas GN1, Calcutt NA, Frizzi K, Rocha-González HI2 Granados-Soto V1, Murbartián J1.

1Departamento de Farmacobiología, Cinvestav, Sede Sur, México, D.F., México. Calzada de Los Tenorios #235, Granjas Coapa, Tlalpan, 14330. E-mail: Tel: (55)-54832800 ext:1214.
2Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina del Instituto Politécnico Nacional, México, D.F., México.
3Department of Pathology, University of California San Diego, La Jolla, CA 92093, USA.


Introduction: The Painful Diabetic Neuropathy (PDN) is among the most debilitating consequences of chronic diabetes, with a prevalence estimated up to 34% in diabetic population. Allodynia, sensory loss and motor nerve deficit are included within the symptoms described by diabetic patients. The treatment of PDN is frequently unsatisfactory. It has been suggested that antioxidant therapy could be an approach to relief PDN. The antioxidant drug (-)-epicatechin has shown effects in attenuate inflammatory pain in a mouse model. The aim of this study was to investigate the (-)-epicatechin’s effect on allodynia, sensory loss and motor nerve deficit in rats subjected to painful diabetic neuropathy (PDN). Methods: Female Wistar rats (220-240 g) were injected with streptozotocin (STZ) (50 mg/kg, i.p.) to produce experimental diabetes. Results: After 8 weeks, the chronic treatment with (-)-epicatechin (3 mg/kg, i.p.) prevented tactile allodynia and partially motor nerve conduction velocity (MNCV), but not thermal hypoalgesia displayed in diabetic rats. In addition, chronic treatment with (-)-epicatechin (3 mg/kg, i.p.) did not prevent SOD expression reduction observed in diabetic rats. Finally, the data showed that (-)-epicatechin did not have effects on the motor coordination test and parameters such as glucose and body weight in diabetic rats. Conclusions: Our data suggest that (-)-epicatechin treatment has antiallodynic effects in PDN rats.


Citation Format: Quiñonez-Bastidas GN, Calcutt NA, Frizzi K, Rocha-González HI, Granados-Soto V, Murbartián J (2015) (-)-Epicatechin reduces allodynia in rats with painful diabetic neuropathy. [Abstract]. In: Proceedings of the FAPRONATURA 2015; 2015 Sep 21-25; Topes de Collantes, Sancti Spiritus: CSF. J Pharm Pharmacogn Res 3(Suppl. 1): S94. Abstract nr PPP-02.

Intervención farmacéutica en pacientes menopáusicas en Antofagasta

J Pharm Pharmacogn Res 3(1): 24-36, 2015.

Original Article | Artículo Original

Intervención farmacéutica a pacientes menopáusicas con terapia hormonal de reemplazo en una farmacia comunitaria de Antofagasta

[Pharmaceutical intervention in menopausal patients with hormone replacement therapy in a community pharmacy from Antofagasta]

Alejandrina Alucema1, Silvia C. González1, Ingrid Valenzuela2, Marisela Valdés1*

1Departamento de Ciencias Farmacéuticas, Facultad de Ciencias, Universidad Católica del Norte, Angamos 0610, Antofagasta, Chile.2Farmacias Cruz Verde, Antofagasta, Chile.

Context: Hormone replacement therapy (HRT) is the most widely used treatment for controlling the effects of menopause. This type of therapy causes some drug-related problems (DRP), which requires monitoring to control the negative effects and ensure patient adherence to therapy.

Aims: Perform a pharmacotherapeutic monitoring and educate to menopausal patients in HRT of a community pharmacy from the city of Antofagasta.

Methods: A 98-menopausal patients underwent a pharmaceutical intervention to identify the PRM and its resolution. It was applied to them a survey before and after educational activities about this disease and HRT to determine the knowledge on the subject.

Results: During the pharmacotherapeutic monitoring was determined that 55% of patients using combined HRT. 62 DRPs were detected, of which 43 were resolved (69%); the most were Patient-Pharmacist (73%). The better resolution DRP were DRP 4(b) “frequency of inadequate administration” and DRP 2(a) “no medical indication”. At baseline, 90% had an inadequate level of knowledge about the disease and THR, 8% intermediate, and only 2% adequate. After the implementation of the education strategy, the level of knowledge increased, achieving at the end of the study only intermediate (10%) and adequate (90%) levels.

Conclusions: The results confirm the importance of pharmaceutical intervention for the identification and resolution of DRP and the requirement to establish educational strategies to increase the knowledge about menopause and HRT in menopausal patients.

Keywords: Hormone replacement therapy; menopause; pharmaceutical care.


Contexto: La terapia hormonal de reemplazo (THR) es el tratamiento más utilizado para controlar los efectos del climaterio. Este tipo de terapia ocasiona algunos problemas relacionados con los medicamentos (PRM), por lo que requiere de un seguimiento para controlar los efectos negativos y asegurar la adherencia de la paciente a la terapia.

Objetivos: Realizar un seguimiento farmacoterapéutico y educar a pacientes menopáusicas en THR de una farmacia comunitaria de la ciudad de Antofagasta.

Métodos: A 98 pacientes menopaúsicas se le realizó una intervención farmacéutica para identificar los PRM y su resolución. Se les aplicó una encuesta antes y después de actividades educativas sobre dicha patología y la TRH, para determinar los conocimientos sobre la temática.

Resultados: Durante el seguimiento farmacoterapéutico se determinó que el 55% de las pacientes utilizaba THR combinada. Se detectaron 62 PRM, de los cuales se resolvieron 43 (69%), la mayoría de forma Farmacéutico-Paciente (73%). Los de mejor resolución fueron los PRM 4(b) “frecuencia de administración inadecuada” y PRM 2(a) “ausencia de indicación médica”. Al inicio del estudio el 90% poseía un nivel inadecuado de conocimiento sobre la patología y la THR, 8% intermedio y solo un 2% adecuado. Posterior a la aplicación de la estrategia educativa, el nivel de conocimiento aumentó, logrando al finalizar del estudio sólo niveles intermedio (10%) y adecuado (90%).

Conclusiones: Los resultados confirman la importancia de la intervención farmacéutica para la identificación y resolución de PRM, así como la necesidad de establecer estrategias educativas para elevar el conocimiento sobre la menopausia y la THR en pacientes menopaúsicas.

Palabras Clave: Atención farmacéutica; menopausia; terapia de reemplazo hormonal.

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Citation Format: Alejandrina Alucema, Silvia C. González, Ingrid Valenzuela, Marisela Valdés (2015) Intervención farmacéutica a pacientes menopáusicas con terapia hormonal de reemplazo en una farmacia comunitaria de Antofagasta. [Pharmaceutical intervention in menopausal patients with hormone replacement therapy in a community pharmacy from Antofagasta]. J Pharm Pharmacogn Res 3(1): 24-36.

© 2015 Journal of Pharmacy & Pharmacognosy Research (JPPRes)


J Pharm Pharmacogn Res 2(Suppl. 1): S38, 2014

Special supplement with the abstract book of LATINFARMA 2013

Oral Communication


Presgrave O, Moura W, Caldeira C, Delgado I.

Instituto Nacional de Controle de Qualidade em Saúde (INCQS)/Fundação Oswaldo Cruz (FIOCRUZ), Brasil. E-mail:

Introduction: Brazilian Law 11,794/2008 rules the animal use and created the Council for the Control of Animal Experimentation (CONCEA) which is responsible, among many other activities, for making alternative methods official in Brazil. The Brazilian Center for Validation of Alternative Methods (BraCVAM) was created in order to identify laboratories and the need of validation, as well as organize and make feasible the execution of validation process.

Objectives: Show how BraCVAM expects to work in Brazil and its relation with similar organizations.

Results: BraCVAM will organize studies to be executed by the National Network on Alternative Methods (RENAMA) following OECD Guideline 34 and it will count on two Committees. The first will peer review the results during the validation and the second will evaluate and recommend finished result to CONCEA. RENAMA received a financial support from National Council of Technological and Scientific Development (CNPq) to help starting two lines: 1) introduction of already validated methods and 2) development of a skin model. It will also be used for starting the process of laboratories accreditation in GLP. BraCVAM was already invited for participating as an observer at the International Cooperation on Alternative Test Methods (ICATM) and to join the OECD Guideline Programme.

Conclusions: Creation of BraCVAM and RENAMA will lead Brazil to join countries that search for alternative methods either for experimental and educational purposes. It makes possible to participate on international studies for validation of methods as well as keep mutual evaluation and acceptance with international 3Rs Centers. BraCVAM and RENAMA will contribute to join institutions that work on alternative methods and it will be possible to develop its own validation strategy of new ingredients or products, especially those ones derived from nature. In a similar way, BraCVAM hope to help the development of networks in Latin America and Caribbean.


J Pharm Pharmacogn Res 2(Suppl. 1): S4, 2014

Special supplement with the abstract book of LATINFARMA 2013

Oral Communication


Ricarte Bratti JP, Montrull HL, Meirovich CI, Jaime NJ, Demurtas SL, Brizuela NY.

Universidad Nacional de Córdoba – Fac Cs Medicas – Cátedra de Farmacología. Santa Rosa 1085, Córdoba, Argentina. E-mail:

Introduction: Sepsis is the leading cause of mortality in intensive care. The study of its pathophysiology is essential to try to change the high mortality that this syndrome presents. The multiple organ dysfunction Syndrome (MODS) is a high mortality syndrome caused by sepsis. Cytokines are the main responsible for the inflammatory response in sepsis and MODS, including IL-1, 6 and TNF alpha. MMP-3 is a molecule relatively recent that has not been studied in sepsis yet.

Aim: To assess the predictive power of cytokines on MODS and death.

Material and methods: 48 patients older than 18 years with sepsis criteria who were attended the Hospital Nacional de Clínicas of Cordoba-Argentina have been included. Upon admission blood samples were drawn for the dosage of cytokines.

Results: Patients with MODS had a mean value of IL-6 of 210.10 ± 30.82 pg/mL and for patients without MODS of 155.32 ± 20.84 pg/mL (p=0.135). For MMP-3 MODS patients had an average of 14.57 ± 0.63 mg/mL whereas patients who did not develop MODS reached an average of 9.8 ± 0.83 mg/mL (p<0.0001). Evaluating mortality IL-6 in death patients was a medium term of 203.65 ± 26.64 pg/mL in slight contrast to the survivors, whose average was 161.88 ± 24.38 pg/mL, giving a difference without statistical significance (p = 0.26). Values of MMP-3 in survivors had an average of 10.55 ± 0.76 mg/mL, whereas the average of the deceased was 13.77 ± 0.98 mg/mL (p=0.012).

Conclusions: MMP-3 has shown that if at the time of admission it´s in a high value (Beyond 12 mg/mL) has a prognostic value since it predicts death and organ failure. IL-6 has a tendency to the above, but with nonsignificant results, so more studies are needed with larger numbers of patients.


J Pharm Pharmacogn Res 2(Suppl. 1): S114, 2014

Special supplement with the abstract book of LATINFARMA 2013

Plenary Lecture


Llerena A.

Clinical Research Centre, Extremadura University Hospital and Medical School, Badajoz, Spain.

Hispanic populations are diverse according to their genetic composition resulting from the inter-ethnic crosses between Amerindians, Europeans and Africans. The frequency of CYP2D6 PMs and UMs in Spain is 7-10% and 4.9%, respectively (Llerena et al., 2009). The CEIBA-RIBEF Network Consortium aimed to evaluate the most relevant CYPs genetic polymorphism in different Ibero-American populations (from Spain, South-, Central-Caribe and North-America in a population of almost 6500 Healthy Volunteers included in the CEIBA consortium. Differences have been found, the frequency of CYP2D6 PMs ranged from 6%-3.9% in Nicaraguans-Cuban-Mestizos. The genetic polymorphism of the most studied cytochrome P450, CYP2D6, is among the major determinants of the interindividual and interethnic variability of pharmacokinetics and drug response. Two CYP2D6 phenotypes have been described: “poor metabolizers” (PM), and “extensive metabolizers” (EM) including a group of Ultra-rapid Metabolizers (UMs). CYP2D6, antidepressants discontinuation and suicide. A higher frequency of UMs has been found among individuals who committed suicide (Zackrisson et al, 2010). One explanation for this relationship could be treatment failure with antidepressant drugs metabolized by CYP2D6 (Llerena et al., 2004) widely used to prevent suicide or to treat mood disorders. A complementary explanation could be via the implication of the polymorphic CYP2D6 in the endogenous metabolism. CYP2D6 has been associated with behavioral and clinical risk factors such as personality and vulnerability to psychopathology (Llerena et al., 1993; 2007; Gonzalez et al., 2008; Peñas-Lledó et al., 2009, 2010). Consistently, we found a relationship between UMs and severity of suicide and lifetime history of suicidal behavior among Eating Disordered patients (Peñas-LLedó et al., 2010, 2011, 2012a). Moreover it seems also been related to antidepressant discontinuation as recently shown in Mexican depressive patients (Peñas-LLedó et al 2012b). The pharmacogenetics of CYP2D6 may be a useful tool to predict unexpected side-effects, interactions, or therapeutic failures of many relevant drugs and may explain the interethnic differences observed not only in the response to psychotropic drugs, but also in the vulnerability to psychopathology including suicide.


J Pharm Pharmacogn Res 2(Suppl. 1): S40, 2014

Special supplement with the abstract book of LATINFARMA 2013

Plenary Lecture


Tyndale R.

Toronto, Canada.

The brain has a unique expression profile of drug and toxin metabolizing cytochrome P450 enzymes (CYPs); multiple forms of CYPs have been identified in the brains of different species including rodents, dogs, monkeys and humans. These CYPs are genetically polymorphic, similar to their expression in the liver meaning some people have high levels, while other people have no expression. These CYPs are uniquely expressed and regulated in a cell and brain-region specific manner and can metabolize many centrally relevant compounds including centrally acting drugs, neurotoxins and neurotransmitters. Drugs and toxins that act on the central nervous system (CNS) may be metabolized in situ in the brain, and differences in in situ metabolism may contribute to variation in an individual’s response to drugs and toxins. Studies in artificial in vitro systems, with added cofactors, indicate that brain CYPs have similar substrate specificity and in vitro kinetics to their hepatic forms. We have shown that brain CYPs are metabolically active in situ using a radio-labeled suicide inhibitor, which takes advantage of the brain CYP metabolic activity of the animal, injected directly into the brain of a living rat. We have also subsequently demonstrated in vivo, using a similar brain inhibitor or induction approach, that enzymes within the brain can alter drug effect. This is illustrated using CYP2B inactivation of the anesthetic propofol within the rat brain and its resulting impact on sedation, CYP2B activation of a neurotoxic pesticide chlorpyrifos and its alteration of neurotoxicity. Likewise we have shown that brain CYP2D activation of codeine to morphine is important to the early time points for analgesia, and that brain CYP2D may importantly alter risk for Parkinson’s disease through its ability to inactivate neurotoxins such as MPTP. These results indicate that brain CYPs are actively able to metabolize CNS acting drugs and neurotoxins and can contribute significantly to local drug response. The induction of brain CYPs by nicotine and alcohol, and higher levels in the brains of smokers and alcoholics, suggests that in addition to pharmacogenetic variation, commonly used drugs could also alter responses to centrallyacting drugs and toxins. More broadly these studies indicate that brain CYPs are active in situ and have sufficient local enzymatic activity to meaningfully alter the pharmacology of centrally acting drugs and neurotoxins.