Pharmacokinetic studies are performed to examine the absorption, distribution, metabolism and excretion of a drug under investigation in healthy volunteers and/or patients. Data obtained from such studies are useful for the design and conduct of subsequent clinical trials. Such studies also provide useful information for the appropriate and safe conduct of clinical trials and for the evaluation of the mechanism of action in human subjects. They are also necessary for appropriate analysis and evaluation of the efficacy and safety data obtained in clinical trials for new drug development and in postmarketing clinical trials. Outcomes of clinical pharmacokinetic studies are useful for determining the appropriate use of medicines according to patient characteristics, such as disease and genotype of drug-metabolizing enzymes, and for predicting the influence of pharmacokinetic drug interactions. The results can also provide information for therapeutic drug monitoring. Development of a new medicine may be achieved, thereby avoiding unnecessary studies. Recently, a growing body of information obtained from different studies conducted around the globe showed a striking rise in healthcare expenditures and the developing countries are not exception. Previous studies conducted in Pakistan showed that a considerable portion of the healthcare costs goes to medicine price. The present dissertation was the first detailed investigation in the relationship between the patient’s socioeconomic status and physician’s choice on multisource solid oral drugs. Such association had not been fully investigated in developing countries, particularly in Pakistan. My dissertation work will provide the information about important aspect and parameters involved in Pharmacokinetic studies.The purpose of this research was to evaluate Pharmacokinetic parameters of a combination formulation of Vildaglipton and metformin hydrochloride50/1000 mg tablet of an established branded formulation.One set of parallel study design was employed in healthy normal rabbits as well as in Alloxan induced diabetic rabbits.The other set of parallel study design was employed in healthy male human subjects as well as in diabetic patients.The concentrations of Vildagliptonand metformin hydrochloride in blood plasma were analyzed using High Performance Liquid Chromatographic (HPLC) technique. The plasma concentration-time curves were used to obtain the different pharmacokinetic parameters. Six healthy rabbits, six diabetic rabbits, twelve diabetic Pakistani patients and twelve healthy Pakistani subjects were selected to participate in this study. A single dose, open label parallel study design was employed in all study subjects. In this study, a oncedaily dose of metformin HCl 1000 mg and vildagliptin 50 mg was used in human subjects, as this allowed assessment of the full pharmacokinetic profile of metformin HCl and vildagliptin over 24 hours at the maximum individual dose. All the rabbits, weighing between 1.25 to 1.5 kg, were given combined dose of drugs metformin HCl 70 mg per 1.5 kg and vildagliptin 15 mg per 1.5 kg orally. Blood samples were withdrawn at predetermined intervals of 0, 0.25, 0.50, 1, 2, 3, 4, 5, 6, 8, 10 and 12 hours from a marginal ear vein puncture. The concentrations of vildagliptin and metformin HCl in blood plasma were analyzed using High Performance Liquid Chromatographic (HPLC) technique and using developed and validated method. The concentration of drugs in blood plasma were determined using standard calibration curves of metformin HCl and vildagliptin having concentrations 50, 100, 200, 500 and 750 ng/mL for vildagliptin and 250, 500, 1000, 2500 and 3750 ng/mL for metformin HCl. The pharmacokinetic parameters were calculated by using different pharmacokinetic formulae. Data is shown as arithmetic mean±SD. The aim of this work was to develop and validate a simple, rapid, more sensitive, more accurate and precise method for simultaneous determination of metformin HCl and vildagliptin in formulations and blood serum. Furthermore, its applications for studying and comparison of pharmacokinetic parameter in Pakistani population among healthy and diabetic individuals along with healthy and diabetic rabbits were analyzed. No significant difference was observed in pharmacokinetic parameters for healthy and diabetic individuals among the humans and the rabbits. There was no statistically significant difference for the treatment values. In both of groups healthy and diabetic pharmacokinetic parameters were equal in terms of rate and extent of absorption. There was no significant difference of drugs absorption and clearance in healthy and diabetic Pakistani subjects.
The paper examines the dynamics of The Gambian National Youth Service Scheme (NYSS) founded in 1996 through the efforts of Nigeria’s National Youth Service Corps (NYSC) Scheme. Though modeled after the NYSC, it has ventured into things NYSC has not. One of these was its most recent partnership with the IOM to curb recurrent illicit migration of The Gambian youths. The questions are, has this aspect of Nigeria-The Gambia history been documented? Has Nigerian Scheme gone into partnership with the IOM in the enterprise like The Gambian counterpart? Since its establishment, how many times has NYSC adjusted to changing realities? In what theoretical contexts could one frame the argument of the NYSS/ IOM partnership and what lessons does that holds for NYSC and similar youths’ services in Africa in the century? In addressing the problem, the paper adopts the qualitative method of historical research and gleans on evidence from diverse sources. It foregrounds its argument on the ideas of the National Youth Service as “Moral Equivalent of War”, “Service- Learning” and “A Way of Strengthening Ties among the People of the World” espoused by William James, John Dewey, and Rosenstock-Huessy. It concludes by charging NYSC and similar services to adjust to meet the current challenges of African youth and society
Introduction: Molecular characterisation of the breast cancer has allowed for targeted therapies that are improving outcomes. The gains achieved by these treatments have fuelled the search for other targets, including cyclin-dependent kinase inhibitors such as p21. p21 expression in breast cancer has been shown to be variably associated with clinical and pathological parameters in different populations. It is possible that either methodological or biological differences underlie these variations.
Objective: The current study sought to determine the association of p21 expression and clinico-pathological parameters in breast cancer patients at the Aga Khan University Hospital in Nairobi, Kenya.
Methods: Clinically annotated tissue samples were obtained in a consecutive fashion. Specimen were immunohistochemically stained for p21 expression with clinicopathological data extracted for corresponding cases. p21 expression was assessed against age, parity, menopausal status, body mass index, hormonal receptor status, tumour size and grade. Distribution of mean p21 score was assessed for normality and data were analysed using Kruskall-Wallis test, chi-square and Fisher's exact test at an alpha level of 0.05. They were presented in form of tables, charts and photomicrographs.
Results: Ninety-eight cases were included in the study. Mean age was 47.55 years with mean parity 2.96 live births. A slight majority of patients were pre-menopausal (56.3% versus 42.5%). Average body-mass index was 29.69 kilograms per square metre. Majority of patients had invasive ductal carcinoma (87.6%) that was moderate-to-high grade (92.7%), 2 centimetres or larger (95%), with lymphovascular invasion (70.4%), and vi hormone-receptor positive. Mean expression of p21 at 1:100 dilution was approximately 20% was statistically significant with tumour size.
Conclusion: The findings of the current study demonstrate a possible association of p21 expression with tumour size. The demonstration of a trend towards p21 loss with increasing body mass index may benefit from exploration with a larger dataset.