Department of Pharmacology
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Item Acute Oral Toxicological Profile of Croton membranaceus Mull. Arg. Aqueous Stem Extract, a Herbal Treatment for Benign Prostate Hyperplasia, in Male Sprague–Dawley Rats(Journal of Toxicology, 2024) Afriyie, D.K.; Ameyaw, E.O; Appiah-Opong, R.; et al.Croton membranaceus Mull. Arg. is a traditional medicinal plant frequently employed in Ghana for the treatment of benign prostatic hyperplasia and prostate cancer. The objective of this study was to determine the acute oral toxicity of the aqueous stem extract of Croton membranaceus (CMASE) in male Sprague-Dawley (S-D) rats. The acute toxicity of CMASE was evaluated using S-D rats randomly divided into four groups of five animals each. Tree groups (low dose, median dose, and high dose) of rats received single oral doses of CMASE (1000, 2500, and 5000 mg/kg body weight, respectively) using an oral gavage. Te control group was given distilled water. After 14 days of daily observations, hematological, biochemical, and histopathological analyses were conducted on the rats. From the results obtained, doses of CMASE up to 5000 mg/kg did not cause death or induce any clinical indications of toxicity during the study period. Also, the mean body weight and the hematological indices assessed were not significantly affected by the various doses of CMASE compared to the control group. However, serum uric acid and creatinine levels decreased significantly (p < 0.001) 14 days after the extract administration. Serum liver function enzyme levels, including alkaline phosphatase (ALP), alanine aminotransferases (ALT), and aspartate aminotransferases (AST), and serum proteins (total proteins and albumin) exhibited significant (p < 0.001) non-dose-dependent changes (increases and decreases) in treated groups compared to the controls. Other biochemical indices, however, did not differ significantly between the treated groups and the controls. The gross pathological and histological analysis of the heart, liver, and kidney tissues did not reveal any significant changes in histoarchitecture. The oral LD50 of CMASE in rats was greater than 5000 mg/kg, indicating that the extract was relatively safe. It must, however, be used with care as a substitute for the roots.Item Acute Oral Toxicological Profile of Croton membranaceus Mull. Arg. Aqueous Stem Extract, a Herbal Treatment for Benign Prostate Hyperplasia, in Male Sprague–Dawley Rats(Journal of Toxicology, 2024) Afriyie, D.K.; Ameyaw, E.O.; Appiah-Opong, R.; et al.Croton membranaceus Mull. Arg. is a traditional medicinal plant frequently employed in Ghana for the treatment of benign prostatic hyperplasia and prostate cancer. The objective of this study was to determine the acute oral toxicity of the aqueous stem extract of Croton membranaceus (CMASE) in male Sprague-Dawley (S-D) rats. The acute toxicity of CMASE was evaluated using S-D rats randomly divided into four groups of five animals each. Tree groups (low dose, median dose, and high dose) of rats received single oral doses of CMASE (1000, 2500, and 5000 mg/kg body weight, respectively) using an oral gavage. Te control group was given distilled water. After 14 days of daily observations, hematological, biochemical, and histopathological analyses were conducted on the rats. From the results obtained, doses of CMASE up to 5000 mg/kg did not cause death or induce any clinical indications of toxicity during the study period. Also, the mean body weight and the hematological indices assessed were not significantly affected by the various doses of CMASE compared to the control group. However, serum uric acid and creatinine levels decreased significantly (p < 0.001) 14 days after the extract administration. Serum liver function enzyme levels, including alkaline phosphatase (ALP), alanine aminotransferases (ALT), and aspartate aminotransferases (AST), and serum proteins (total proteins and albumin) exhibited significant (p < 0.001) non-dose-dependent changes (increases and decreases) in treated groups compared to the controls. Other biochemical indices, however, did not differ significantly between the treated groups and the controls. The gross pathological and histological analysis of the heart, liver, and kidney tissues did not reveal any significant changes in histoarchitecture. The oral LD50 of CMASE in rats was greater than 5000 mg/kg, indicating that the extract was relatively safe. It must, however, be used with care as a substitute for the roots.Item Anxiolytic-like efects of Pseudospondias microcarpa hydroethanolic leaf extract in zebrafsh: Possible involvement of GABAergic and serotonergic pathways(Natural Products and Bioprospecting, 2023) Adongo, D.W.; Benneh, C.K.; Kukuia, K.K.E.; et al.Pseudospondias microcarpa is used in ethnomedicine to manage central nervous system diseases. The hydroethanolic extract (PME) from the leaves of the plant has shown anxiolytic-like properties in mice anxiety models. However, its efects in chronic anxiety models and possible mechanism(s) of action were not studied. Therefore, the current study evaluated the anxiolytic-like mechanisms of PME in zebrafsh models of anxiety. The zebrafsh light dark test (LDT) and novel tank test (NTT) were employed to assess the anxiolytic-like efects of PME (0.1, 0.3, 1.0 mg mL−1), fuox etine (3× 10−5 mg mL−1) and diazepam (1.5× 10−7 mg mL−1). The chronic unpredictable stress (CUS) test was used to further evaluate the extract’s anxiolytic-like properties. The potential mechanisms of anxiolytic action of the extract was evaluated after pre-treated with fumazenil, granisetron, methysergide, or pizotifen, all at 1× 10−3 mg mL−1. The extract signifcantly decreased anxiety behaviours in the NT and LD tests. These observed efects of the extract were however counteracted by fumazenil, granisetron, methysergide and pizotifen pre-treatment. In addition, PME treat ment signifcantly reversed CUS-induced anxiety behaviours in zebrafsh. Results show that PME possesses anxiolytic like efects possibly through interaction with serotonergic and gamma-aminobutyric acid mediated pathwaysItem Delivery of Vaccines via the Nasal Route(Springer Link, 2023) Amponsah, S.K.; Amoafo, E.B.Several methods, including novel formulations and production systems, have been proposed as ways to improve drug delivery. Nasal delivery of drugs is traditionally employed when local effects (allergies, congestion, and respiratory illnesses) and/or systemic effects (pain treatment) are required. Over the last couple of years, the nasal route has been sought as a site for vaccine delivery. Data suggests that when vaccines are administered via the nasal route, they elicit powerful immune system responses. There are a number of vaccines that have been developed for nasal administration, some of which include Nasalflu, FluMist®, and Coronavac, among others. The nasal route for delivering vaccines has many merits; however, a few drawbacks limit the use of this route. Nonetheless, scientists are still trying to exploit this route as a potential for vaccine administration.Item Sub-effective doses of a bendroflumethiazide-imipramine combination offer greater synergistic antidepressant effect compared to a bendroflumethiazide-fluoxetine combination: an isobolographic analysis(HSI Journal, 2023) Mensah, J.A.; Kukuia, K.K.E.; Amoateng, P.; et al.Background: Bendroflumethiazide is often prescribed with fluoxetine or imipramine for patients with both depression and hypertension. However, there is little data on the potential interactions between these drugs. Objective: The objective of this study was to investigate the potential antidepressant effects of bendroflumethiazide, as well as sub-effective dose combinations of bendroflumethiazide with fluoxetine or imipramine. Methods: Forced swimming and tail suspension tests were used to investigate the behavioural effects of bendroflumethiazide [5-20 mg/kg; per os (p.o], imipramine (3-30 mg/kg; p.o) and fluoxetine (3-30 mg/kg; p.o). Mean immobility, swimming, climbing, curling, and swinging scores were measured. Median effective dose (ED50) values were calculated from the immobility scores. The antidepressant effect of the combination of bendroflumethiazide with imipramine or fluoxetine at sub-effective doses was then investigated. Isobolographic analyses were performed on these combinations to investigate possible synergism, additivity or antagonism. Results: Bendroflumethiazide produced a significant diminution in mean immobility scores, suggestive of an antidepressant-like effect, while increasing swimming, climbing and swinging scores. Imipramine and fluoxetine also exhibited antidepressant-like effects. A combination of bendroflumethiazide and imipramine at sub-effective doses showed a synergistic antidepressant-like effect with an interaction index of 0.31 as did the bendroflumethiazide-fluoxetine combination (interaction index: 0.41). Conclusion: This study demonstrated the acute antidepressant-like effect of bendroflumethiazide. Moreover, bendroflumethiazide imipramine combinations offer greater synergy when compared to bendroflumethiazide-fluoxetine combinations.Item Therapeutic Drug Monitoring and Clinical Toxicology: Challenges and Future Directions(Springer, Cham, 2023) Amponsah, S.K.; Pathak, Y.V.Therapeutic drug monitoring (TDM) is the clinical practice of measuring levels of drugs in the plasma, serum, or blood at predetermined times or intervals in an effort to maintain blood concentration of a drug within optimum range. Drugs that are usually monitored are those with low therapeutic indices, drugs that have irreversible adverse effects, as well as drugs used in the treatment of diseases whose symptoms are similar to the toxic effects of the drug. TDM is useful in detecting compliance and non-compliance to drug therapy in patients. It also provides a means of detecting treatment failure. Clinical toxicology is the study of the physiological effects of toxic agents, their mechanism of action, and ways of managing these effects. Furthermore, clinical toxicology helps in the identification of chemicals, drugs, or toxins that may affect patients. Even though TDM and clinical toxicology are useful, they come with some limitations. Some of the assays used in TDM and clinical toxicology lack sensitivity. Taking samples at the right time is another challenge associated with TDM and clinical toxicology. Inaccuracies from sampling site and handling of samples prior to analysis can affect results. Some drugs also have active metabolites that might not be detected by TDM and clinical toxicological assays. Additionally, TDM and clinical toxicology are expensive to undertake. Indeed, the significance of TDM and clinical toxicology in clinical practice cannot be overemphasized. Nonetheless, more research can be done on alternate sampling matrices such as saliva and dried blood spot. These matrices would make TDM and clinical toxicology more convenient and easy to do. There is the need for better interpretation of results obtained from TDM and clinical toxicological assays. Hence, health professionals need to be trained and re-trained on appropriate interpretation of TDM and clinical toxicological results so patients are managed appropriately.Item Absorptive capacity and innovation generation in higher education institutions: the mediating role of inter-functional coordination(The Learning Organization, 2023) Asiedu, M.A.; Anyigba, H.; Doe, J.K.Purpose – The purpose of this paper is to theoretically broaden the knowledge-based view (KBV) by examining the significant intermediary role that inter-functional coordination (IFC) plays in acquiring new knowledge and exploiting it throughout the entire higher education institution (HEI) community for innovation generation (INNG). Design/methodology/approach – Data collected from a survey of 282 lecturers purposively selected from the business schools of 20 HEIs in the Greater Accra region of Ghana was analyzed using partial least squares structural equation model to test the hypotheses proposed for the study. Findings – The results revealed that IFC significantly predicts teamwork and strong relationships across faculties, departments and units, and has a positive effect on the generation of innovations such as improved curricula, enhanced academic instruction and quality research output. Practically, the findings advise HEI managers to invest resources and efforts at building strong relationships that facilitate collaboration, trust and interactions among varying faculties, departments and units. This will enhance inter-functional knowledge sharing in academia to sustain a competitive advantage and continued relevance. Research limitations/implications – There are limitations that must be considered when interpreting and generalizing the quantitative results of this study. Data were collected from faculty staff of 20 public and private HEIs in the Greater Accra region of Ghana. Although the majority of HEIs are clustered in this region, the results may still not be representative of all HEIs in Ghana. Practical implications – Managers of HEIs are advised to commit to ensuring the management of IFC to promote knowledge sharing across faculties and departments. Managers are also advised to ensure that staff are made to be responsible for their cooperative and integrative teamwork. They are also advised to ensure that faculty and departmental goals are aligned with the overall goals of the university. Staff may also be encouraged to act as partners and not just employees through rewards, incentives and recognition packages. Social implications – Attention should be focused on creating lateral relations among faculty and department members to achieve internal social capital. They are advised to invest resources and efforts in building a culture of teamwork and connectedness through strong informal networking that facilitate collaboration between faculties and departments while cultivating a shared vision throughout the university. Originality/value – The main contribution of this paper is that it theoretically extends the KBV by empirically broadening the scope of absorptive capacity (ACAP) beyond its dimensions to include the “collaborative mechanism” (IFC) through which knowledge can be holistically exploited. The paper also contributes to existing literature by examining the intermediary role played by IFC in the relationship between ACAP and INNG in the HEIs domain which has been least discussed in the ACAP literature.Item Pharmaceutical and pharmacokinetic evaluation of a newly formulated multiparticulate matrix of levodopa and carbidopa(ADMET & DMPK, 2023) Imbeah, E.P.; Adi-Dako, O.; N’guessan, B.B; et al.Levodopa is routinely co-administered with carbidopa in the management of Parkinson’s disease. Although the aforementioned combination therapy is effective, there may be fluctuating plasma levels of levodopa after oral administration. We formulated and evaluated the kinetic characteristics of the chitosan-pectin-based multiparticulate matrix of levodopa and carbidopa. Pectin was extracted from the cocoa husk, and the chitosan-pectin-based matrix was prepared by wet granulation. Formulations were evaluated for drug-excipient compatibility, drug content, precompression properties and in vitro release. For pharmacokinetic evaluation, rats were put into groups and administered either chitosan-pectin based matrix of levodopa/carbidopa, Sinemet® CR or levodopa/carbidopa immediate release powder. Rats were administered the different formulations of levodopa/carbidopa (20/5 mg/kg) per os every 12 hours. The pharmacokinetic parameters of levodopa were estimated for the various treatment groups. The percentage content of levodopa and carbidopa in the various formulations was within the acceptance criteria. The AUC0-24 for levodopa/carbidopa multiparticulate matrix (Formulation 3: 484.98 ± 18.70 µg.hr/mL); Formulation 4: 535.60 ± 33.04 µg.hr/mL), and Cmax (Formulation 3: 36.28 ± 1.52 μg/mL; Formulation 4: 34.80 ± 2.19 μg/mL) were higher than Sinemet® CR (AUC0-24 262.84 ± 16.73 µg.hr/mL and Cmax 30.62 ± 3.37 μg/mL). The t1/2 of the new formulation was longer compared to Sinemet® CR.Item Bioanalysis of aminoglycosides using high-performance liquid chromatography(Admet, 2022) Amponsah, S.K.; Boadu, J.A.; Dwamena, D.K.; Opuni, K.F.M.Aminoglycosides are broad-spectrum antibiotics used in the treatment of gram-negative bacterial infections. Due to their nephrotoxic and ototoxic potential (narrow therapeutic index), the use of aminoglycoside for clinical indications requires monitoring. The objective of this review was to identify relevant literature reporting liquid chromatographic methods for the bioanalysis of aminoglycosides in both preclinical and clinical settings/experiments. Data on liquid chromatographic methods were collected from articles in an online academic database (PubMed, Science Direct, Scopus, and Google Scholar). All 71 articles published from 1977 to 2020 were included in the review. Reversed-phase liquid chromatography was the most used method for the bioanalysis of aminoglycosides. Fluorescence or ultraviolet detection methods were mostly used from 1977 to 2002 (51 articles), while mass spectrometry was predominantly used as a detector from 2003 to 2020 (15 articles). Sixty-seven articles reported calibration ranges, which varied significantly for the various drugs assayed: some in the range of 0.1-0.5 ng/mL and others 1250-200000 ng/mL. Also, 61 articles reported R2 values (0.964-1.0) for almost all analytes under consideration. Sixty-three articles reported percent recoveries mostly between 61.0 % to 114.0 %, with only two articles reporting recoveries of 4.9 % and 36 %. Out of the 71 reviewed articles, 56 reported intermediate precision values ranging between 0.331 % to 19.76 %, which is within the acceptable limit of 20 %. This review will serve as a guide for research and/or routine clinical monitoring of aminoglycosides in biological matrices.Item A Pharmacokinetic Evaluation of a Pectin-Based Oral Multiparticulate Matrix Carrier of Carbamazepine(Hindawi, 2021) Amponsah, S.K.; Yeboah, S.; Kukuia, K.K.E.; N’guessan, B.B.; Adi-Dako, O.Background. Carbamazepine is a drug used in the treatment of neurological disorders such as epilepsy. However, due to its erratic absorption, oral bioavailability is often poor. There is, therefore, the need to develop alternative formulations for carbamazepine with better pharmacokinetic characteristics. Aim. .e aim of this study was to formulate an oral modified-release multiparticulate matrix of carbamazepine from cocoa pod husk (CPH) pectin and evaluate the pharmacokinetic profile of this formulation using in vitro and in vivo models. Methods. CPH pectin was extracted from cocoa pod husks with hot aqueous and citric acid solutions. Oral multiparticulate carbamazepine matrices were formulated from CPH pectin cross-linked with calcium. .e formulation was evaluated for carbamazepine content and release profile in vitro. For in vivo pharmacokinetic profile estimation, rats were put into 4 groups of 5 animals each to receive carbamazepine multiparticulate matrix formulations A and B, carbamazepine powder, and Tegretol CR®. Animals in each group received 200 mg/kg of each drug via the oral route. Maximum plasma concentration (Cmax), area under the concentration-time curve (AUC), elimination rate constant (Ke), and terminal half-life (t1/2) of the formulations were estimated by noncompartmental analysis. Results. .e pectin extraction from fresh cocoa pod husks using hot aqueous and citric acid solutions gave pectin yields of 9.63% and 11.54%, respectively. .e drug content of carbamazepine in CPH pectin formulations A and B was 95% and 96%, respectively. .ere was controlled and sustained release of carbamazepine for both formulations A and B in vitro. AUC0⟶36 (176.20 ± 7.97 µg.h/mL), Cmax (8.45 ± 0.71 μg/mL), Tmax (12 ± 1.28 h), and t1/2 (13.75 ± 3.28 h) of formulation A showed a moderately enhanced and comparable pharmacokinetic profile to Tegretol CR® (AUC0⟶36: 155 ± 7.15 µg.h/mL, Cmax: 8.24 ± 0.45 μg/mL, Tmax: 8.0 ± 2.23 h, and t1/2: 13.51 ± 2.87 h). Conclusion. Findings from the study suggest that formulations of CPH pectin had the potential to control and maintain therapeutic concentrations of carbamazepine in circulation over a period of time in the rat model.
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