Comparison of the Efficacy, Tolerability and Side Effect Profile of Vildagliptin-Metformin with Metformin-GlibenclamideMamong Nigerian.

BACKGROUND: The use of fixed dose combination oral antidiabetic drugs (OADs) in the therapeutic management of type 2 diabetes mellitus (DM) patients is becoming popular among clinicians. Reduced pill burden with fixed combination OADs is generally perceived to improve adherence and efficacy. The aim of this study was to compare the efficacy, tolerability and side effects (SEs) profile of vildagliptin-metformin (VM) combination with metformin-glibenclamide (MG) combination in type 2 DM patients at the Aminu Kano Teaching Hospital (AKTH). METHODS: A descriptive prospective open-labeled comparative out-patient study of type 2 DM patients spanning over three months with 60 Patients assigned to two treatment groups - VM (Group 1) and MG (Group 2) of 30 patients each. Parameters measured at baseline, 6 weeks and 12 weeks of study included demographic and anthropometric data; fasting plasma glucose (FPG) level; 2-hour post-prandial (2-hrPPG) glucose; liver function tests (LFTs); Electrolyte, Urea and Creatinine (EUCr); and fasting plasma lipids. Glycated haemoglobin (HbA1c) was measured at baseline and at 12 weeks of the study. A p-value of <0.05 was considered to be significant. RESULTS: There was improvement in FPG, 2hr PPG, HbA1c in all subjects in both groups at the end of the study (6.44±0.79mmol/ l, 8.80±1.16mmol/l and 7.22±1.20% respectively in group 1(VM); and 6.40±0.83mmol/l, 9.29±1.39 and 7.25±0.96% respectively for group 2(MG). There was a significant improvement in body mass index (BMI) of subjects in group 1 (30.02±4.16 at baseline, 29.71±4.12 at study end) compared to those in group 2 (31.98±6.32 at baseline, 32.62±6.30 at study end), p=0.04. At the end of the study, the efficacy of VM (HbA1C-7.22±1.20%) was comparable to that of MG (HbA1c-7.25±0.96), P=0.92. The tolerability of MG (attrition rate 6.7%) was better than that of VM (attrition rate 13%), although this difference was not statistically significant P=0.16. The subjects on VM experienced more gastrointestinal (GIT) side effects compared to those on MG. The major SEs experienced by those on MG were hypoglycaemia and weight gain. VM was less tolerated and had more GIT side effects than MG. CONCLUSION: The use of single pill combination oral antidiabetic medications is associated with improved efficacy.

CONTEXTE: L'utilisation d'associations fixes d'antidiabétiques oraux (ADO) dans la prise en charge thérapeutique des patients atteints de diabète sucré (DM) de type 2 est en train de devenir populaire parmi les cliniciens. La réduction du fardeau de la pilule avec des ADO à combinaison fixe est généralement perçue comme améliorant l'observance et l'efficacité. Le but de cette étude était de comparer l'efficacité, la tolérabilité et le profil d'effets secondaires (ES) de l'association vildagliptine - metformine (VM) avec l'association metformine - glibenclamide (MG) chez des patients atteints de DM de type 2 à l'hôpital universitaire Aminu Kano (AKTH). MÉTHODES: Une étude descriptive prospective ouverte comparative ambulatoire de patients atteints de diabète de type 2 s'étalant sur trois mois avec 60 patients répartis en deux groupes de traitement - VM (groupe 1) et MG (groupe 2) de 30 patients chacun. Les paramètres mesurés au départ, 6 semaines et 12 semaines d'étude comprenaient des données démographiques et anthropométriques ; taux de glucose plasmatique à jeun (FPG); Glycémie post-prandiale 2 heures (2-hrPPG) ; tests de la fonction hépatique (LFT); électrolyte, urée et créatinine (EUCr); et les lipides plasmatiques à jeun. L'hémoglobine glyquée (HbA1c) a été mesurée au départ et à 12 semaines de l'étude. Une valeur p < 0,05 a été considérée comme significative. RÉSULTATS: Il y avait une amélioration de la FPG, 2h PPG, HbA1c chez tous les sujets dans les deux groupes à la fin de l'étude (6,44 ± 0,79 mmol/l, 8,80 ± 1,16 mmol/l et 7,22 ± 1,20 % respectivement dans le groupe 1 (VM) et 6,40 ± 0,83 mmol/l, 9,29 ± 1,39 et 7,25 ± 0,96 % respectivement pour le groupe 2 (MG). Il y avait une amélioration significative de l'indice de masse corporelle (IMC) des sujets du groupe 1 (30,02 ± 4,16 au départ, 29,71 ± 4,12 à la fin de l'étude) par rapport à ceux du groupe 2 (31,98 ± 6,32 à l'inclusion, 32,62 ± 6,30 à la fin de l'étude), p = 0,04. À la fin de l'étude, l'efficacité de la VM (HbA1C-7,22 ± 1,20 %) était comparable à celle de MG (HbA1c-7,25 ± 0,96), P= 0,92. La tolérance de MG (taux d'attrition 6,7 %) était meilleure que celle de VM (taux d'attrition 13 %), bien que cette différence n'ait pas été statistiquement significative P= 0,16. Les sujets sous VM ont présenté plus d'effets secondaires gastro-intestinaux (GIT) que ceux sous MG. Les principaux effets secondaires ressentis par ceux sous MG étaient l'hypoglycémie et la prise de poids. La VM était moins tolérée et avait plus d'effets secondaires GIT que MG. CONCLUSION: L'utilisation de médicaments antidiabétiques oraux combinés à une seule pilule est associée à une efficacité améliorée. Mots clés: Diabète, Efficacité, Metformine-Glibenclamide, Tolérabilité, Vildagliptine-Metformine.

Antiplasmodial activity-aided isolation and identification of quercetin-4'-methyl ether in Chromolaena odorata leaf fraction with high activity against chloroquine-resistant Plasmodium falciparum.

The present study was undertaken to evaluate the antiplasmodial activity of Chromolaena odorata leaf extract and gradient fractions through in vivo and in vitro tests, aimed at identifying its antiplasmodial constituents. Sub-fractions obtained from the most active gradient fraction were further tested for cytotoxicity against THP-1 cells, chloroquine-sensitive (HB3) and chloroquine-resistant (FCM29) Plasmodium falciparum. Our results showed the dichloromethane gradient fraction was most effective, significantly (P < 0.05) suppressing infection by 99.46% at 100 mg/kg body weight. Amongst its 13 sub-fractions (DF1-DF13), DF11 was highly active, with IC50 of 4.8 and 6.74 µg/ml against P. falciparum HB3 and FCM29, respectively. Cytotoxicity of DF11 was estimated to be above 50 µg/ml, and its separation by column chromatography yielded a flavonoid which was characterized as 3, 5, 7, 3' tetrahydroxy-4'-methoxyflavone from its spectroscopic data. It significantly suppressed infection (65.43-81.48%) in mice at 2.5-5 mg/kg doses and compared favourably with the effects of chloroquine and artemisinin. It may therefore serve as a useful phytochemical and antiplasmodial activity marker of C. odorata leaves, which exhibit potential for development as medicine against malaria.

Antihyperglycaemic activity of the stem-bark extract of Tamarindus indica L. on experimentally induced hyperglycaemic and normoglycaemic Wistar rats.

Diabetes is the most common endocrine disease and its prevalence is reaching epidemic proportion worldwide. In 2002, WHO Expert Committee on diabetes mellitus recommended an urgent and further evaluation of the folkloric methods of managing the disease. In response to this recommendation, several medicinal plants are currently being investigated for their hypoglycaemic activity and one of such plants is Tamarindus indica. Tamarindus indica is a slow growing tree that is resistant to strong winds and perennial. The stem-bark extract of the plant is used locally for the management of diabetes. The stem-bark extract of Tamarindus indica L. was investigated for its hypoglycemic action on experimentally induced hyperglycaemic Wistar rats using a single dose of alloxan monohydrate (150 mg kg(-1) IP). The oral LD50 of the extract was found to be greater than 5,000 mg kg(-1). Phytochemical screening revealed the presence of carbohydrates, glycosides, saponins, flavonoids, cardiac glycosides, tannins, alkaloids and triterpenes. The 1000 mg kg(-1) dose of the extract lowered the blood glucose level significantly (p < 0.05) at the 4th, 8th and 16th h. The 500 mg kg(-1) lowered the BGL significantly (p < 0.05) throughout the study. In the oral glucose load method the 1000 mg kg(-1) dose of the extract significantly (p < 0.05) lowered elevated blood glucose at the 3rd and 5th. The 500 mg kg(-1) lowered the blood glucose from the 1st to the 5th, while the 250 mg kg(-1) also lowered the blood glucose level but only significantly at the 5th h. The extract is practically non toxic when administered orally. The stem-bark extract of Tamarindus indica Linn significantly lowered elevated Blood Glucose concentration (BGL) in the experimental animal models, while the crude extract was able to prevent an elevation in BGL when used in the oral glucose load model.

Pharmacological evaluation of Ipomoea asarifolia (Desr.) against carbon tetrachloride-induced hepatotoxicity in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ipomoeaasarifolia (Desr.) Roem. and Schult. is used traditionally in some parts of Africa for the treatment of a variety of diseases. This study attempts to validate its hepatoprotective activity by evaluating the prophylactic and curative properties of the methanolic extract of Ipomoea asarifolia (IA) leaves. MATERIALS AND METHODS: Liver damage was induced by administering 0.5 ml/kg of an equal mixture of carbon tetrachloride (CCl(4)) in olive oil intraperitoneally on alternate days, for 5 days and the plant extract was given orally daily, for 7 days at doses of 100, 200 and 400 mg/kg. RESULTS: Pre-treatment with the extract significantly (P<0.05) decreased CCl(4)-induced elevation in serum levels of alanine transaminase, aspartate transaminase, alkaline phosphatase, triglycerides, bilirubin and cholesterol, better than the standard drug silymarin at 100 mg/kg. In the curative study, IA significantly (P<0.05) reversed CCl(4)-induced liver damage, comparable to silymarin. Hepatoprotective potential was further supported by decrease in pentobarbitone sleeping time and improved hepatic tissue histopathology. CONCLUSION: These results indicate that I. asarifolia leaves have potent hepatoprotective activity against CCl(4)-induced hepatic damage in rats.

Studies on the possible mechanisms of antidiabetic activity of extract of aerial parts of Phyllanthus niruri.

CONTEXT/OBJECTIVES: The effects of methanol extract of aerial parts of Phyllanthus niruri L. (Euphorbiaceae), an antidiabetic herb, on glucose absorption and storage in diabetes were studied to elucidate the mechanisms of blood glucose lowering and glycemic control in diabetes. METHODS: The effect of chronic oral administration of the extract on glycemic control was evaluated in alloxan diabetic rats using blood glucose lowering and post-prandial glucose suppression activities as well as effects on hemoglobin glycation and body weight. Effects on glucose mobilization and storage were assessed using the weight and glycogen content of liver isolated from treated diabetic rats, while in vitro inhibition of α-amylase and α-glucosidase enzyme activities were used as indices of effect on glucose absorption. RESULTS: Results showed that the extract lowered blood glucose, suppressed postprandial rise in blood glucose following a glucose meal, reduced hemoglobin glycation and increased absolute and relative weights as well as glycogen content of liver in diabetic rats. Treatment with the extract also ameliorated the decrease in body weights caused by the diabetic disease. In vitro, the extract inhibited α-amylase (IC50: 2.15 ± 0.1 mg/mL) and α-glucosidase (IC50: 0.2 ± 0.02 mg/mL) activities. DISCUSSION AND CONCLUSION: These findings suggest that aerial parts of P. niruri may owe their blood glucose lowering properties to inhibition of glucose absorption and enhancement of glucose storage.

Microbiological and mucociliary properties of the ethanol extract of Hymenocardia acida on selected respiratory clinical isolates.

The antimicrobial property of the ethanol leaf extract of Hymenocardia acida (H. acida) on some opportunistic respiratory pathogens was evaluated in this study. We also assessed the activity of the extract on tracheal mucociliary activity using murine tracheal mucus exudation and mucociliary motility in pigeons as experimental models. Phytochemical screening of the extract was done; and acute toxicity of the extract in mice was carried out using Lorke's method for estimation of its median lethal dose. Results show the presence of carbohydrates, saponins, tannins, flavonoids, alkaloids, resins, and balsams in the extract and the absence of anthraquinones, terpenes, and sterols. Results of the acute toxicity test showed that the extract was slightly toxic, with an estimated median lethal dose of 1,767.77 mg/kg body weight. At 50, 100, and 200 mg/kg body weight of H. acida, tracheal mucus exudation was increased by 14.29, 19.24, and 33.82%, respectively. The effect on mucociliary velocity was dose-dependent as 50, 100, and 200 mg/kg body weight of the extract led to increased ciliary activity by 7.69, 61.5, and 81.6%, respectively. The effects of the extract (200 mg/kg body weight) on mucus exudation and clearance were significant (p < .05) and higher than the effect of ammonium chloride. Although the extract did not inhibit the growth of C. albicans and K. pneumoniae, it exhibited moderate antimicrobial activity against Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, and Staphylococcus aureus. These findings show the mucociliary activity and antimicrobial properties of H. acida ethanol extract, and justify its use in the treatment of airway disorders.

Effect of oral administration of aqueous whole extract of cassytha filiformis on haematograms and plasma biochemical parameters in rats.

INTRODUCTION: We evaluated the sub-chronic toxicity of the aqueous herbal extract prepared from Cassytha filiformis and administered daily for 28 days at dose levels (250, 500, and 1000 mg/kg bw) in male wistar albino rats. The LD50 of the aqueous extract was determined. METHODS: The effects on body weights, organ weights, and certain haematological and plasma biochemical parameters were measured as indices of organ toxicity. RESULTS: The aqueous extract did not affect plasma glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT); however, a significant reduction in alkaline phosphatase (ALP) level occurred in all the treated groups. It also did not affect the electrolytes (Na , Cl and K ), total and direct bilirubin, creatinine, and glucose level. The aqueous extract elicited hypercholesterolaemic effects, but it did not affect the Hb, WBC, RBC, PVC, platelets, MCH, MCHC, MCV levels and differential counts (lympocytes, neutrophils, monocytes, eosinophils and basophils). It also reduced the body weight gain and absolute weight of the kidneys. The relative weights of the heart and lungs in some animal groups were equally reduced. The acute toxicological evaluation of the plant extract revealed an oral LD50 value greater than 500 mg/kg bw. CONCLUSION: This study suggests that aqueous extract of C. filiformis administered at normal therapeutic doses is not likely to produce severe toxic effects on some organs or haematological and biochemical indices in rats.

Effects of anticonvulsants on acute cypermethrin poisoning in mice and rats.

Male albino mice were given 35 mg cypermethrin/kg bw followed immediately by 1.0, 2.5 or 5 mg diazepam/kg, 5, 10 or 20 mg phenobarbitone/kg, or 10, 25 or 50 mg diphenylhydantoin/kg ip in dose groups of 10 mice each. Effectiveness of therapy was assessed by alleviation of effects and survival percentage. Rat brains implanted with electroencephalographic (EEG) and electromyograhic electrodes were given 58 mg cypermethrin/ kg followed by 5 mg diazepam/kg, 20 mg phenobarbitone/kg, or 50 mg diphenylhydantoin/kg. Diazepam at 5 mg or 20 mg phenobarbitone/kg produced 100% survival and alleviated all the signs of poisoning while diphenylhydantoin produced 80% survival at 50 mg/kg. The antidotes antagonised desynchronization of EEG waves produced in rats exposed to cypermethrin. These results suggest involvement of GABA in the mechanism of cypermethrin action in addition to its established effect on the sodium ion channel.