Sub-Chronic Effect of Co-Administration of Methformine and Amilodipine on Some Haematological Indices in Experimental Animal (Wistar Rats)

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.