TABLE OF CONTENT
Title page i
Declaration ii
Certification iii
Dedication iv
Acknowledgement v
Table of content vi
List of table vii
List of figures viii
Abstract ix
CHAPTER ONE
1.0 Introduction 1
1.1 Background of study 1
1.2 Statement of Problems 2
1.3 Justifications 4
1.4 Aims 4
1.5 Research Objectives 5
1.6 Research Hypothesis 5
1.7 Significance of research 5
CHAPTER TWO
2.0 Literature review 6
2.1 Metformin 6
2.1.1 Mechanism of metformin 7
2.1.2 Pharmacological properties of metformin 10
2.1.3 Side effects and contra-indications of metformin 11
2.1.4 Therapeutic application of metformin 13
2.2 Vitamin B12: biochemistry, deficiency and anaemia 15
2.3 Relationship between metformin and vitamin B12 22
2.4 Metformin and haemolytic anaemia 24
2.5 Diagnosis of anaemia 25
2.6 Efficacy of Metformin 27
2.7 Amlodipine 31
2.7.1 Chemistry 31
2.7.2 Mechanism of action 31
2.7.3 Side effects 32
2.7.4 Pharmacokinetics 32
2.8 Angiotensin Converting Enzyme Inhibitors 33
2.9 Reference range of haematological parameters of rats 34
2.10 Comparative haematology of rat and human 36
CHAPTER THREE
3.1 Study Design 39
3.2 Preparation of animals 40
3.3 Sample size determination 40
3.4 Reagent Kits/Drug Preparation and Dosage 40
3.5 Dosage 41
3.6 Sample collection 43
3.7 Measurement of variables . 43
3.8 Ethical consideration 46
3.9 Statistical analysis 47
CHAPTER FOUR
4.1 Result 48
42.Differential white blood cell counts in controls and tests groups 49
CHAPTER FIVE
5.0 Discussion 58
5.1 Conclusion 61
5.2 Recommendation 62
References 63
Appendix I 75
Appendix II 76
LIST OF TABLES
Table 1: Haematological parameters in control, Co-administration of Metformin and Amlodipine treated 39
LIST OF FIGURES
Figure 1: Shows mechanism of action of metformin 10
Figure 2: Shows Pie chat representation of Packed cell volume of control, Co-administration of metformin and amlodipine treated Wistar Rats 54
Figure 3: Shows Histogram representation of Hemoglobin and red blood cell count of control, Co-administration of metformin and amlodipine treated Wistar Rats 55
Figure 4: Shows Histogram representation of red cell indicies of control, Co-administration of metformin and amlodipine treated Wistar Rats 56
Figure 5: Shows Histogram representation of platelet and white blood cell count of control, Co-administration of metformin and amlodipine treated Wistar Rats 57
ABSTRACT
Metformin, which belongs to the biguanide class, is one of the most generally used oral hypoglycemic agents. It has been used for more than 50 years and was approved by the US Food and Drug Administration (FDA) in 1994 (American Diabetes Association, 2009) whereas Amlodipine is a long acting dihydropyridine calcium channel blocker, which is used in the treatment of angina to lower the BP (Blood pressure). the aim is to know the effect of co-administration of this two drugs in Wistar rats. To assess the MCV,MCH,MCHC level of experimental animal and that of control group after combined administration with amilodipine and metformin. Animals were randomly grouped into Two (A and B) groups, each groups contains eight (8) animals. Group A was administered normal saline; Group B was administered combined administration with amilodipine (0.00264mg/ml/132g) and metformin (0.0438mg/ml/132g) once daily for 30days after 2 weeks of acclamatization. Each group of rats was allowed to have free access to water ad libitum and standard rat chow (SRC) throughout the experimental period. Blood was collected from the Jugular vein at the end of the experiment to determine the full blood count of each animal. There was a significant reduction (p≤0.05) in hemoglobin level, RBC, PCV and increase in WBC and decrease in PLT count, and with increase in MCV, MCH with no difference in MCHC after co-administration of Metformin and Amlodipine in Wistar Rat as compared to control. These findings suggests that Co-administration of Metformin and Amlodipine causes decrease in red cell dependent parameters gradually leading to anaemia with long term usage thus regarded as a hematotoxicity agent to the blood profile.
