Submitted by Simone Souza (simonecgsouza@hotmail.com) on 2017-09-20T13:55:03Z No. of bitstreams: 1 DISS_2014_Morenna Alana Giordani.pdf: 1859265 bytes, checksum: b5d9642bcb74a3b47527bc37b687bab3 (MD5) / Approved for entry into archive by Jordan (jordanbiblio@gmail.com) on 2017-09-26T12:41:05Z (GMT) No. of bitstreams: 1 DISS_2014_Morenna Alana Giordani.pdf: 1859265 bytes, checksum: b5d9642bcb74a3b47527bc37b687bab3 (MD5) / Made available in DSpace on 2017-09-26T12:41:05Z (GMT). No. of bitstreams: 1 DISS_2014_Morenna Alana Giordani.pdf: 1859265 bytes, checksum: b5d9642bcb74a3b47527bc37b687bab3 (MD5) Previous issue date: 2014-08-25 / CNPq / A Cedrela odorata L. (cedro-rosa) foi selecionada para a avaliação antidiabética in vivo, com base nos resultados obtidos em triagem in vitro, realizada com várias plantas citadas em levantamento etnofarmacológico na região do Vale do Juruena – Mato Grosso. Nesta triagem foram avaliadas a inibição da alfa-glicosidase e a capacidade antioxidante pelo sequestro do radical DPPH dos extratos hidroetanólicos. O extrato hidroetanólico da entrecasca de C. odorata L. (EHeCo) apresentou CI50 e CD50 na avaliação inibidora da alfa-glicosidase e antioxidante de 84,6 e 3,7 μg/mL respectivamente, muito abaixo do controles positivos acarbose e vitamina C (5115,5 e 7,9 μg/mL) respectivamente. O fingerprint do EHeCo mostrou a presença de ácido gálico, (-)-galocatequina e (+)-catequinas. Os testes de toxicidade aguda (10 a 5000 mg/kg) e de toxicidade subcrônica (500 mg/kg), mostraram que o extrato apresentou baixa toxicidade nas doses avaliadas. Nos testes de avaliação antidiabética subcrônica, foram utilizados animais diabéticos induzidos com estreptozotocina (40 mg/kg em tampão citrato 0,01 M pH 4,5 iv) e não diabéticos. Os animais diabéticos foram tratados com 250 e 500 mg/kg de EHeCo (DT250 e DT500) por 21 dias e os resultados comparados com o grupo diabético tratados com veículo – DMSO 2% (DC) e com o grupo controle positivo (metformina 500 mg/kg - DMet). Não foram observadas alterações no peso corporal, consumo de ração e água, volume urinário de 24h, glicemia, glicosúria e ureia urinária. O nível de triglicérides plasmáticos foi reduzido nas duas doses avaliadas (N = 132 ± 15; DC = 123 ± 15; DT250 = 73 ± 10#; DT500 = 78 ± 8#; DMet = 142 ± 10 mg/dL, #p<0,05). Após 21 dias de tratamento com EHeCo houve redução na concentração de malonaldeído no sangue (N = 1,9 ± 0,3; DC = 5,6 ± 0,5; DT250 = 3,3 ± 0,3; DT500 = 2,9 ± 0,5#; DMet = 3,9 ± 1,0 μmol/L, #p<0,05) e aumento da atividade das enzimas superóxido dismutase (N = 42,3 ± 0,3; DC = 40,9 ± 0,7; DT250 = 60,7 ± 1,8#; DT500 = 60,8 ± 1,1#; DMet = 42,0 ± 0,4 U/L, #p<0,05) e glutationa peroxidase (N = 16,2 ± 0,5; DC = 11,4 ± 0,7*; DT250 = 15,6 ± 0,5#; DT500 = 14,8 ± 0,3#; DMet = 12,2 ± 0,5 103 U/L, *p<0,05 vs N, #p<0,05 vs DC). O efeito do EHeCo sobre a tolerância à glicose, foi avaliada após uma sobrecarga de glicose, amido e sacarose, sendo o extrato administrado nas mesmas doses dos experimentos subcrônicos, 30 minutos antes da sobrecarga de carboidratos. Foram utilizadas floridzina (DF) como controle positivo para o teste em que a sobrecarga foi glicose, e a acarbose (DA), quando a sobrecarga foi de sacarose ou amido. O extrato, nas duas doses reduziu o pico glicêmico e também a área sobre a curva (glicemia x tempo de avaliação) quando a sobrecarga foi de glicose (N = 16253 ± 318; DC = 37666 ± 2347*; DT250 = 32353 ± 1467; DT500 = 27666 ± 1423#; DF = 25033 ± 1241# mg/dL x 120 minutos, *p<0,05 vs N, #p<0,05 vs DC). Quando a sobrecarga foi de sacarose, o extrato na dose de 500 mg/kg reduziu o pico glicêmico após 30 minutos (N = 138 ± 3; DC = 437 ± 39*; DT250 = 294 ± 38; DT500 = 243 ± 69#; DA = 253 ± 22# mg/dL, *p<0,05 vs N, #p<0,05 vs DC) sem redução da área sobre a curva. O EHeCo não teve efeito sobre a glicemia dos animais que receberam amido. O EHeCo apresentou efeitos anti-hiperglicemiante, hipolipidêmico e antioxidante, mostrando o potencial terapêutico da entrecasca de C. odorata no tratamento do diabetes e das complicações relacionadas à doença. / Cedrela odorata L. (cedro-rosa) was selected for the antidiabetic in vivo evaluation, based on the results obtained from an in vitro screening performed with various plants mentioned in an ethnopharmacological survey in the region of Vale do Juruena - Mato Grosso, Brazil. This screening aimed to evaluate the inhibition of alpha-glucosidase and the antioxidant capacity by DPPH radical sequestering of hydroethanolic extracts. The hydroethanolic extract of the inner stem bark of Cedrela odorata L. (HeECo) showed IC50 and DC50 in the evaluation of inhibition of alpha-glucosidase and an antioxidant capacity of 84.7 e 3.7 μg/mL, respectively, well below the positive control acarbose and vitamin C (5115.5 e 7.9 μg/mL), respectively. The fingerprint of EHeCo showed the presence of gallic acid, (-)- gallocatechin and (+)- catechins. Tests for acute and sub-chronic toxicity showed that the extract presented low toxicity at the evaluated doses. In the sub-chronic antidiabetic evaluation tests, streptozotocin-induced diabetic rats (40 mg/kg in 0.01 M citrate buffer pH 4.5 iv) and non-diabetic rats were used. Diabetic animals were treated with 250 and 500 mg/kg HeECo for 21 days and the results were compared with the vehicle-treated diabetic group - 2% DMSO (DC) and the positive control group (metformin - DMet). No changes were observed in body weight, food and water intake, urine volume, blood glucose, glucosuria and urinary urea. The triglyceride level was reduced at the two doses (N = 132 ± 15; DC = 123 ± 15; DT250 = 73 ± 10#; DT500 = 78 ± 8#; DMet = 142 ± 10 mg/dL, #p<0,05). After 21 days of treatment with HeECo, the concentration of malondialdehyde in the blood was reduced (N = 1.9 ± 0.3; DC = 5.6 ± 0.5; DT250 = 3.3 ± 0.3; DT500 = 2.9 ± 0.5#; DMet = 3.9 ± 1.0 μmol/L, #p<0.05) and the activity of superoxide dismutase (N = 42.3 ± 0.3; DC = 40.9 ± 0.7; DT250 = 60.7 ± 1.8#; DT500 = 60.8 ± 1.1#; DMet = 42.0 ± 0,4 U/L, #p<0.05) and glutathione peroxidase increased (N = 16.2 ± 0.5; DC = 11.4 ± 0.7*; DT250 = 15.6 ± 0.5#; DT500 = 14.8 ± 0.3#; DMet = 12.2 ± 0.5 103 U/L, *p<0.05 vs N, #p<0.05 vs DC). The HeECo effect on glucose tolerance was assessed after a glucose, starch and sucrose overload, the extract being administered at the same dose as in the sub-chronic experiment, 30 minutes before the carbohydrate overload. Phloridzin (DF) was used as positive control for the test in which the overload consisted of glucose, and acarbose (DA), when the overload was sucrose or starch. The extract, at both doses reduced the glycemic peak and also the area under the curve (N = 16253 ± 318; DC = 37666 ± 2347*; DT250 = 32353 ± 1467; DT500 = 27666 ± 1423#; DF = 25033 ± 1241# mg/dL x 120 minutes, *p<0.05 vs N, #p<0.05 vs DC) when the overload was glucose. When the loading was sucrose, the extract at a dose of 500 mg/kg, reduced the peak blood glucose after 30 minutes without reduction in the area under the curve (N = 138 ± 3; DC = 437 ± 39*; DT250 = 294 ± 38; DT500 = 243 ± 69#; DA = 253 ± 22# mg/dL, *p<0.05 vs N, #p<0.05 vs DC). The HeECo had no effect on blood glucose levels of the animals receiving starch. The HeECo showed antihyperglycaemic, hypolipidemic and antioxidant, showing the therapeutic potential of the inner stem bark of C. odorata in the treatment of diabetes and disease-related complications.

Background: More than 5.5 million South Africans aged 30 years and older are at risk of chronic disease by virtue of their triglyceride levels (Maritz, 2006:101). Dyslipidaemia is common in westernized and industrialized communities (Steyn et al., 2000:720), especially so for South Africa, where burden of disease data show dyslipidaemia to be the second most prevalent of all the chronic conditions in the country (Council for Medical Schemes, 2006:48). It is therefore no surprise that at 3.3 per cent hipolipidaemics ranked second highest based on prevalence percentage per therapeutic group in the 2005 Mediscor medicines review on South African medical claims data (Bester et al., 2005:8-11). Hipolipidaemic drugs subsequently also ranked second highest for expenditure per therapeutic group, achieving a total expenditure of 5.8 per cent. Objective: The purpose of this study was to characterise the usage and cost of hipolipidaemic drugs in the private health care environment in South Africa based on various categories, including age, sex, prescriber type and generic indicator. Methods: A quantitative retrospective drug utilisation review was performed using dispensing records from a medicine claims database. Data for a two-year period (1 Jan. 2005 to 31 Dec. 2006) were used. Hipolipidaemic medicine usage was analysed according to five patient age strata: patients younger than 9 years, 10 ≤ 19 years, 20 ≤ 45 years, 46 ≤ 59 years and older than 59 years. Basic descriptive statistics such as frequencies and arithmetic mean (average) were used to characterise the study sample, and were calculated using the Statistical Analysis System (SAS®) for Windows 9.1® program (SAS Institute Inc., 2002-2003). Results: The database consisted of 19 860 593 and 21 473 062 medicine item claims for 2005 and 2006 respectively, at a total cost of R 1 893 376 921.00 (for 2005) and R2 046 944 383.00 (for 2006). Patients receiving hipolipidaemic medicine items represented about 7.2% of the total number of patients on the database in both 2005 and 2006. About 47% of the study population in both 2005 and 2006 was female, compared to 53% males. Hipolipidaemics represented between 3.1% (N = 19 860 593) and 3.3% (N = 21 473 062) of the total number of items claimed during the study period. The total cost of hipolipidaemics accounted for between 5.6% (N = R1 893 376 921.00) and 5.8% (N = R2 046 944 383.00) of the total cost of all medications claimed during the study period. The average cost per item of hipolipidaemics was R170.63 ± 70.19 in 2005 compared to R167.08 ± 71.93) in 2006. HMG-CoA reductase inhibitors formed the leading therapeutic class in hipolipidaemic medicine items in all age groups on the database, except for children aged 0 ≤ 9 years, where the “others” group, in particular cholestyramine (Questran Lite 4 mg) was claimed more frequently. Of the items claimed for both study periods, simvastatin was the most commonly claimed, accounting for 45.35% (n = 284 232) and 46.21% (n = 325 970) respectively of the number of hipolipidaemic items claimed, at a total cost of 30.97% (n = R33 119 294.18) and 31.38% (n = R36 983 938.41) for 2005 and 2006 respectively. Non-substitutable and generic hipolipidaemic medicine items carried the largest percentage of prevalence and cost in both study periods for both sex categories and all age groups. The majority of claims for hipolipidaemic medicine items were prescribed by general medical practitioners, followed by “other prescribers” and then by cardiologists. Only a small number of prescriptions claimed were prescribed by thoracic surgeons and even fewer by pharmacotherapists and pharmacists. Trade name products that were mostly prescribed were Lipitor and Adco-Simvastatin. Of all the hipolipidaemic drugs utilised on the database, only three active ingredients (bezafibrate, simvastatin and pravastatin) had generic equivalents available at the time of the study. With total substitution (100%) of these three drugs with the average price of the available generic hipolipidaemic equivalents on the database, a cost saving of R1 744 462.27 or 1.63% (N = R106 943 348.53) was possible in 2005. In 2006, a total cost saving of R1 526 985.79 or 1.30% (N = R117 862 631.87) was calculated. Conclusion: The study highlighted the most commonly prescribed hipolipidaemics within a sub-population of South African patients. The high average cost per prescription of hipolipidaemic drugs indicates that they are relatively expensive in comparison to other medications. Generic (and therapeutic) substitution should be investigated as potential cost-saving mechanisms in the private health care sector of South Africa. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2010.

Background: More than 5.5 million South Africans aged 30 years and older are at risk of chronic disease by virtue of their triglyceride levels (Maritz, 2006:101). Dyslipidaemia is common in westernized and industrialized communities (Steyn et al., 2000:720), especially so for South Africa, where burden of disease data show dyslipidaemia to be the second most prevalent of all the chronic conditions in the country (Council for Medical Schemes, 2006:48). It is therefore no surprise that at 3.3 per cent hipolipidaemics ranked second highest based on prevalence percentage per therapeutic group in the 2005 Mediscor medicines review on South African medical claims data (Bester et al., 2005:8-11). Hipolipidaemic drugs subsequently also ranked second highest for expenditure per therapeutic group, achieving a total expenditure of 5.8 per cent. Objective: The purpose of this study was to characterise the usage and cost of hipolipidaemic drugs in the private health care environment in South Africa based on various categories, including age, sex, prescriber type and generic indicator. Methods: A quantitative retrospective drug utilisation review was performed using dispensing records from a medicine claims database. Data for a two-year period (1 Jan. 2005 to 31 Dec. 2006) were used. Hipolipidaemic medicine usage was analysed according to five patient age strata: patients younger than 9 years, 10 ≤ 19 years, 20 ≤ 45 years, 46 ≤ 59 years and older than 59 years. Basic descriptive statistics such as frequencies and arithmetic mean (average) were used to characterise the study sample, and were calculated using the Statistical Analysis System (SAS®) for Windows 9.1® program (SAS Institute Inc., 2002-2003). Results: The database consisted of 19 860 593 and 21 473 062 medicine item claims for 2005 and 2006 respectively, at a total cost of R 1 893 376 921.00 (for 2005) and R2 046 944 383.00 (for 2006). Patients receiving hipolipidaemic medicine items represented about 7.2% of the total number of patients on the database in both 2005 and 2006. About 47% of the study population in both 2005 and 2006 was female, compared to 53% males. Hipolipidaemics represented between 3.1% (N = 19 860 593) and 3.3% (N = 21 473 062) of the total number of items claimed during the study period. The total cost of hipolipidaemics accounted for between 5.6% (N = R1 893 376 921.00) and 5.8% (N = R2 046 944 383.00) of the total cost of all medications claimed during the study period. The average cost per item of hipolipidaemics was R170.63 ± 70.19 in 2005 compared to R167.08 ± 71.93) in 2006. HMG-CoA reductase inhibitors formed the leading therapeutic class in hipolipidaemic medicine items in all age groups on the database, except for children aged 0 ≤ 9 years, where the “others” group, in particular cholestyramine (Questran Lite 4 mg) was claimed more frequently. Of the items claimed for both study periods, simvastatin was the most commonly claimed, accounting for 45.35% (n = 284 232) and 46.21% (n = 325 970) respectively of the number of hipolipidaemic items claimed, at a total cost of 30.97% (n = R33 119 294.18) and 31.38% (n = R36 983 938.41) for 2005 and 2006 respectively. Non-substitutable and generic hipolipidaemic medicine items carried the largest percentage of prevalence and cost in both study periods for both sex categories and all age groups. The majority of claims for hipolipidaemic medicine items were prescribed by general medical practitioners, followed by “other prescribers” and then by cardiologists. Only a small number of prescriptions claimed were prescribed by thoracic surgeons and even fewer by pharmacotherapists and pharmacists. Trade name products that were mostly prescribed were Lipitor and Adco-Simvastatin. Of all the hipolipidaemic drugs utilised on the database, only three active ingredients (bezafibrate, simvastatin and pravastatin) had generic equivalents available at the time of the study. With total substitution (100%) of these three drugs with the average price of the available generic hipolipidaemic equivalents on the database, a cost saving of R1 744 462.27 or 1.63% (N = R106 943 348.53) was possible in 2005. In 2006, a total cost saving of R1 526 985.79 or 1.30% (N = R117 862 631.87) was calculated. Conclusion: The study highlighted the most commonly prescribed hipolipidaemics within a sub-population of South African patients. The high average cost per prescription of hipolipidaemic drugs indicates that they are relatively expensive in comparison to other medications. Generic (and therapeutic) substitution should be investigated as potential cost-saving mechanisms in the private health care sector of South Africa. / Thesis (M.Pharm. (Pharmacy Practice))--North-West University, Potchefstroom Campus, 2010.