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Sub-chronic Effect Of Co-administration Of Methformine And Amilodipine On Some Haematological Indices In Experimental Animal
[A CASE STUDY OF WISTAR RATS]
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From the above table,
Km of rats= 6
Km of human= 37
For Amlodipine, Human dose= 10mg/70kg
1kg=10/70
=0.14mg/kg
AED of Amilodipine= 0.14×(6/37)
=0.02mg/kg
Average weight of experimental Animal is 132g(0.132kg)
If 0.02mg of Amlodipine is administered per kg.bw,(0.02×0.132)mg of Amlodipine was administered to 0.132kg of experimental animals.
Therefore, 0.00264mg of Amlodipine was administered once daily.
For Metformin, Human dose= 0.332g/70kg
therefore, 0.332g of tablet = 70000g
therefore, 132g of rat will take 132 x 0.332g of tablet
= 0.0438g
0.000849g was dissolved in 1ml of distilled water
for the actual dosing 1:1
0.0438mg of metformin + 0.00264mg of amlodipine in 1ml of distilled water administered to the rats daily
3.6 Sample collection
Blood samples:
At the end of 30days the rats in group A and B will be subjected to an overnight fast which they will be anaesthesized all the animals will be sacrificed by Jugular puncture. 5mls of blood samples was collected into EDTA bottle.
3.7 Measurement of Variables
Determination of full blood count was done as described by Barbara et al., 2006.
The hematology sysmex counter Kx-21 was used
The sysmex Kx-21 employs three detector blocks and two kinds of reagents for blood analysis. The WBC count is measured by WBC detector block using the DC detection method. The RBCs count and Platelets is taken by the RBCs detector block, also using DC detection method. This instrument works in two analysis modes: whole blood mode and prediluted mode. Whole blood mode is the mode of analyzing collected blood sample in the whole blood status. The pre-diluted mode is used in analyzing a minute amount of blood collected from the ear lobe or finger tip. The mode, which will be chosen for this study is the whole blood mode. Here, the RBCs are counted in 1µl of whole blood by a DC detection method and the Hb is measured as a volume in gram per 1dl of whole blood using a non-cyanide haemoglobin analysis method (CDC, 2005).
PROCEDURE FOR RBC COUNT BY AUTOMATION
1. Blood is aspirated from the vacutainer bottle containing the whole blood into the machine.
2. 4µl of blood is diluted in 1:500 by adding 1.996mml of the diluents, and brought to the mixing chamber as diluted sample.
3. Out of the 1:500 dilution samples, 40µl is measured and rediluted by 1.960ml of diluents, then transferred to the RBCs transducer chamber.
4. 250 µl of the sample in the RBCs transducer chamber is apirated through the aperture, then the RBCs are counted by the DC detection method (CDC, 2005).
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ABSRACT - [ Total Page(s): 1 ]ABSTRACTMetformin, 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 ... Continue reading---
APPENDIX A - [ Total Page(s): 1 ]APPENDIXAPPENDIX 1:    MATERIAL USED1% Ammonium oxalate10% Formalin salineAbsorbent paperAutomatic pipetteBrilliant cresyl blueCounting chamber Cyanmethaemoglobin standardDrabkin’s ReagentEDTA sample containerHematoxylin and Eosin stainKhan tubes/rackLeisfhmann stainLight microscopeMicrohaematocrit centrifugeNormal salinePasteur pipettePipette tipsRotary microtomeSpectrophotometerTimer Turk’s solution Universal sample bottle ... Continue reading---
APPENDIX B - [ Total Page(s): 1 ]APPENDIX IITable 1: haematological parameters in control, Metformine treated and Amilodipine treated Rats (Values are expressed as mean ± Standard error of means)                Group A(1): control (untreated), Group B(2): co-administration of Metformin 0.00264/ml/132g and Amlodipine 0.000849/ml/132g at a single dose for 30 daysPARAMETERS    GROUP A    GROUP  BPacked cell volume (%)   44.16±2.83   38.47±3.53Red blood cell count (x1012/L)   7 ... Continue reading---
LIST OF TABLES - [ Total Page(s): 1 ]LIST OF TABLESTable 1: Haematological parameters in control, Co-administration of Metformin and Amlodipine treated ... Continue reading---
LIST OF FIGURES - [ Total Page(s): 1 ]LIST OF FIGURESFigure 1: Shows mechanism of action of metformin Figure 2: Shows Pie chat representation of Packed cell volume of control, Co-administration of metformin and amlodipine treated Wistar Rats      Figure 3: Shows Histogram representation of Hemoglobin and red blood cell count of control, Co-administration of metformin and amlodipine treated Wistar Rats  Figure 4: Shows Histogram representation of red cell indicies of control, Co-administration of metformin and amlodipine t ... Continue reading---
TABLE OF CONTENTS - [ Total Page(s): 1 ]TABLE OF CONTENTTitle page  Declaration Certification Dedication    Acknowledgement    Table of content    List of table List of figures    Abstract   CHAPTER ONE1.0 Introduction   1.1 Background of study  1.2 Statement of Problems        1.3 Justifications   1.4 Aims    1.5 Research Objectives     1.6 Research Hypothesis    1.7 Significance of research  CHAPTER TWO2.0 Literature review   2.1 Metformin   2.1.1 ... Continue reading---
CHAPTER ONE - [ Total Page(s): 2 ]CHAPTER ONE1.0Â Â Â INTRODUCTION1.1 Background of the studyMetformin, 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). Currently, many clinical practice guidelines for patients with type 2 diabetes, including the American Diabetes Association (ADA), the European Association for the Study of Diabetes ... Continue reading---
CHAPTER TWO - [ Total Page(s): 12 ]The current use of serum Vitamin B12 level relies on several different range points for Vitamin B12 status. Serum Vitamin B12 level under 148 pmol/L are said to be deficient, low/borderline levels are interpreted from levels between 148-220 pmol/L (Mazokopakis and Starakis, 2012). Normal ranges of Vitamin B12 serum range from 220- 800 pmol/L, levels that exceed this are rarely suspicious in cause, although excessive B12 serum may be a marker of myloproliferative disorders (Pernicova and Korbonit ... Continue reading---
CHAPTER FOUR - [ Total Page(s): 6 ]CHAPTER FOUR4.0 Results4.1 Hematological parameter in control and test groups   As summarized in table 1, the mean RBC counts were 7.62 ± 2.83 x1012/L for the control and 6.53 ± 0.57 x1012/L for co-administration of metformin and amlodipine fed groups respectively. Although, decrease in RBC counts was observed in the treated (co-administration of metformin and amlodipine) dose group, these were statistically significant compared to control groups (student t test P0.05) higher in the tr ... Continue reading---
CHAPTER FIVE - [ Total Page(s): 2 ]CHAPTER FIVE5.0 DiscussionMetformin (1,1-dimethylbiguanide) is the most widely used drug to treat type 2 diabetes, and is one of only two oral anti-diabetic drugs on the World Health Organization (WHO) list of essential medicines (American Diabetes Association, 2009). Amlodipine is a long acting dihydropyridine calcium channel blocker, which is used in the treatment of angina to lower the BP. Co-administration of Metformin and Amlodipine have been discovered to lead to vitamin B12 deficiency. Al ... Continue reading---
REFRENCES - [ Total Page(s): 4 ]Senol, M.G., Sonmez, G., Ozdag, F. and Saracoglu, M. (2008). Reversible myelopathy with vitamin B12 deficiency. Singapore Medical Journal. 49(11): 330-332.Srinivasan, S., Ambler, G.R., Baur, L.A., Garnett, S.P. and Tepsa, M. (2006). Randomized, controlled trial of metformin for obesity and insulin resistance in children and adolescents: improvement in body composition and fasting insulin. Journal of Clinical Endocrinology and Metabolism. 91: 2074-2080. Sterne, J. (1957). Du nouveau dans les anti ... Continue reading---
