Master of Science (M.Sc.) Theses and Dissertations
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- ItemOpen AccessPharmacokinetic interactions involving selected antimalarial and antimicrobial agents during co-administration in healthy volunteers.(Department of pharmaceutical chemistry, Faculty of pharmacy, Obafemi Awolowo University., 2022) ADEMISOYE Adebusyi AkandeThis study determined the baseline pharmacokinetics of amodiaquine, quinine, itraconazole, piperaquine, their metabolites and evaluated the effect co-administration of rifampicin on the pharmacokinetics of amodiaquine. It also evaluated the bi-directional drug interactions between itraconazole and quinine as well as the effect of clarithromycin on the pharmacokinetics of piperaquine in healthy volunteers. These were with the view to providing information on the magnitude of interactions during co-administration of antimalarials and selected antimicrobial agents. Volunteers were randomly selected and administered single oral dose of amodiaquine (600 mg) and rifampicin (150 mg) daily for five days with concurrent oral single dose amodiaquine (600 mg) after six week wash out period on the 5th day. Another set of volunteers were administered oral single dose quinine (600 mg). Following a three-week wash out period, itraconzole (100 mg) was administered daily for ten days. Blood samples were collected following the 5th dose of itraconazole over a period of 24 hours and during the co-administration of a single oral dose of quinine on the 8th day, while continuing itraconazole drug administration. Another set of volunteers were adminsitered single oral dose of P-Alaxin© consisting piperaquine (320 mg) and dihydroartemisinin (80 mg). Following a five-month wash out period, clarithromycin (500 mg) was given twice daily for five days. A single dose of P-Alaxin© was administered on the 3rd day. In all the cases, blood samples were collected at 0, 1, 2, 4 8, 12, 24, 48 h and analyzed for plasma levels of the administered drugs and their metabolites; 3-hydroxyquinine and hydroxyitraconzole using validated RP-HPLC methods. The difference between pairs were evaluated by student‘s t-test and Wilcoxon matched pair signed rank test. A p-value of <0.05 was considered significant. The values within 80%-125% range of test/reference ratio of the geometric means at 90% confidence intervals were considered bioequivalent. The elimination half-life of amodiaquine declined significantly following concurrent administration with rifampicin (p<0.05), the Cmax and AUC0-48 decreased 2 and 3 folds respectively. The AUC0-48 of desethylamodiaquine increased two folds while the metabolic ratio increased from 1.55 to 2.68. Following concurrent administration of quinine with itraconazole, AUC0-48 and Cmax of quinine increased 3 folds and about 30% percent increase for both Cmax and AUC0-48 of itraconazole. The Cmax, AUC0-48, and T1/2 of piperaquine when concurrently administered with clarithromycin increased significantly (179.41±56.35 ng/ml vs 478.99 ± 148.86 ng/ml; 37,644.56 ± 16.716.95 ng/ml*h vs 104,098.47 ± 53.311.57 ng/ml*h; 247.96 ± 64.98 h vs 468.59±164.94 h) respectively (p<0.05). The Cmax obtained for amodiaquine, quinine and piperaquine fell within 80% 125% bioequivalence range. The study concluded that interactions occurred between amodiaquine and rifampicin; quinine and itraconazole; and piperaquine and clarithromycin which could lead to treatment failure or adverse effects in humans
- ItemOpen AccessComparative Assessment of the Antimalarial Activity of Nephrolepic Undulata, Nephrolepis Biserrata, Platycerium Stemaria and Platycerium Angolense In Mice(The Department of Pharmacognosy, Faculty of Pharmacy, Obafemi Awolowo University, 2022) AKOSILE, Oluwayomi RebeccaThe study determined the in vivo antimalarial activities of methanol extracts of the four ferns namely; Nephrolepis undulata, N. biserrata, Platycerium stemaria, P. angolense in mice, identified the most active fern and determined the relative antimalarial activities of its partitioned fractions. This was with the aim of providing information on the relative antiplasmodial profile of the ferns. The four ferns were collected from different locations on Obafemi Awolowo University, Ile- Ife campus. They were separately air-dried, powdered and the methanol extracts obtained after cold maceration process and afterwards concentrated in vacuo. After preliminary toxicity studies, using Lorke’s method, the four extracts were investigated (100-800 mg/kg) for antimalarial potency against chloroquine-sensitive Plasmodium berghei berghei in mice using the Peters four-day test. Normal saline and chloroquine (10 mg/kg) were negative and positive controls, respectively. The extracts were administered orally. Nephrolepis undulata which displayed the highest antiplasmodial activity was partitioned into solvents of different polarities to give n-hexane, dichloromethane, ethyl acetate and aqueous fractions, which were also tested at 100, 200, 400 and 800 mg/kg. The survival times and percentage survivors of mice were determined after a 28-day observation for mortality. All the results were subjected to statistical analysis using ANOVA with Student Newman Keul’s post hoc test. The methanol extract of Nephrolepis undulata with the least average percentage parasitaemia of 1.40 %, percentage chemosuppression of 71.2 % at the highest dose of 800mg/kg, ED50 and ED90 of 294.27±17.72 and 560.45± 39.5, respectively was the most active and was also comparable (p>0.05) in activity to chloroquine (10 mg/kg), the positive control which gave a percentage parasitaemia of 1.92%. The average percentage parasitaemia of 1.40, 1.58, 2.18, 1.85 % and percentage chemosuppression 71.20, 59.28, 35.60, 52.82 % elicited by Nephrolepis xx undulata, N. biserrata, Platycerium stemaria and P. angolense, respectively at the highest doses tested gave an order of activity N. undulata>P. stemaria > N. biserrata> P. angolense for the four ferns. The comparatively lower percentages chemosuppression of 28.15, 44.98, 46.53, 38.37 % and higher effective doses of 809.06, 692.17, 675.26, 625.23 elicited respectively by n-hexane, dichloromethane, ethyl acetate and the aqueous partitioned fraction of the most active N. undulata suggested that the active antimalarial constituents are acting synergistically. However, the similar high percentage survivor elicited in mice by the dichloromethane fraction with chloroquine, the standard drug may suggest further exploration of N. undulata for its antimalarial constituents. Otherwise, a combination of these four ferns can be explored for further activity in the ferns. It can be deduced from the result of the study that Nephrolepis undulata is the most active fern of the four as antimalarial agent and its active constituents are probably acting synergistically.
- ItemOpen AccessIN-VIVO ANTI-HYPERGLYCAEMIC AND TOXICITY STUDIES OF COMBINATION OF SENECIO BIAFRAE OLIV.&HIERN, XYLOPIA AETHIOPICA DUNAL, CARICA PAPAYA L. AND SPONDIAS MOMBIN L.(Department of Pharmacognosy ,Faculty of Pharmacy ,Obafemi Awolowo University ,Ile Ife, 2022) Bello Oyenike IdayatThis study evaluated the toxicity profile, the in-vitro alpha-amylase and alpha-glucosidase inhibitory activities, and the hyperglycaemia-lowering potential of the methanol extract of combination of Senecio biafrae leaf, Xylopia aethiopica fruit, Carica papaya seed, and Spondias mombin stem bark. This is with a view to establishing its anti-hyperglycaemic efficacy and safety. The plants, S. biafrae leaf, C. papaya seed, and S. mombin were collected from Obafemi Awolowo University while X. aethiopica fruit was purchased from Oja Oba Modakeke, Osun State. The plants were authenticated, air-dried, and mixed in a ratio of 1:1:1:1, extracted using methanol. The methanol extract was estimated for the lethal dose (LD50) and subacute (250, 500, and 1000 mg/kg) toxicity in rats using the modified OECD test guidelines. Blood samples collected via cardiac puncture after the 28 days of successive extract treatment were used for the haematological analysis while serum was used for biochemical analysis during the subacute toxicity study. The anti-hyperglycaemic activity of the methanol extract (0.05, 0.1, 0.25, 0.5, and 1 mg/ml) was assessed by in-vitro alpha-amylase and alpha-glucosidase inhibitory assays with acarbose (0.05, 0.1, 0.25, 0.5 and 1 mg/ml) (positive control) using UV spectrophotometry. In addition, the in-vivo anti-hyperglycemic activity of the methanol extract was separately evaluated at 25, 50, 100, 200 mg/kg and 50, 100 mg/kg, using the glucose-induced hyperglycaemic (FBS ≥ 7 mmol/l) and streptozotocin-treated diabetic (FBS ≥11 mmol/l) rats models, respectively. Glibenclamide (5 mg/kg) and distilled water served as the positive and negative controls respectively. The results were statistically analysed employing one-way analysis of variance (ANOVA), followed by Student Newman Keul's test, with p < 0.05 being regarded significant statistically. The study showed that the estimated lethal dose (LD50) of the methanol extract was greater than 5000 mg/kg. The extract (250, 500, and 1000 mg/kg) gave no significant changes in the blood sugar levels, haematological and biochemical markers in subacute toxicity. It also gave a similar (p > 0.05) alpha-amylase and alpha-glucosidase inhibitory effect to acarbose. The extract (100 mg/kg) demonstrated the highest anti-hyperglycaemic effect with a percentage blood glucose decrease of 19, 40, 43 and 57 % as opposed to glibenclamide (5 mg/kg) which gave 10, 18, 24, and 40 % at 0.5, 1, 2 and 4 h, respectively. In Streptozotocin-treated diabetic rats, the extract (50 mg/kg) gave a percentage anti-diabetic activity of 31, 85 and 85 % in contrast to 14, 56 and 75 % for glibenclamide (5 mg/kg) on days 4, 7, and 10, respectively. The study concluded that the methanol extract of the combination of Senecio biafrae leaf, Xylopia aethiopica fruit, Carica papaya seed, and Spondias mombin stem bark is safe and anti-hyperglycaemic at a lower dose, thereby establishing its anti-hyperglycaemic efficacy and safety.
- ItemOpen AccessInvestigation of some Nigerian ethnomedicinal antidiabetic plants forability to prevent acute hyperglycaemia(Department of Pharmacognosy, Faculty of Pharmacy, Obafemi Awolowo University., 2015) JAIYESIMI, Olakunle AdeboyeThe study screened nine Nigerian ethnomedicinal plants and determined the plant with the greatest ability to prevent hyperglycinemia. it also determined the most active fraction of the plant with this ability. This was with a view to providing information on Nigerian antidiabetic plants with the ability to prevent hyperglycinemia.