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www.wjpps.com Vol 3, Issue 8, 2014. 2207
Siddiqui et al. World Journal of Pharmacy and Pharmaceutical Sciences
DIFFERENCES IN LIPID PROFILE WITH INTERNATIONAL
PRODUCT OF SIMVASTATIN AND LOCAL PRODUCT IN PATIENTS
WITH PRIMARY HYPERLIPIDEMIA
1
Naveed Ali Siddiqui, MBBS, MPhil, 2
Tahira Perveen, 3
Syed Asif Jahanzeb Kazmi,
4
Aziza Khanum, 5
Ambreen.
1
Department of Biochemistry, Bhitai Dental & Medical College, Mirpurkhas, Pakistan.
2
Professor, Department of Biochemistry, University Of Karachi.
3
Assistant Professor, Department of Pharmacology, Mohiuddin Islamic Medical College,
Mirpur, Azad Jammu & Kashmir.
4
Professor, Department of Biochemistry, Al-Tibri Medical College, Karachi, Pakistan
5
Sr.Lecturer, Baqai Medical University, Karachi.
ABSTRACT
Objective: To compare the changes in lipid profile in patients with
primary hyperlipidemia using international and local product of the
lipid lowering drug, Simvastatin. Material and Methods: The study
was conducted at Surgeon Munawar Memorial Hospital, Karachi in
year 2009 -2011. The study was designed to evaluate the effects of
simvastatin on lipid profile, and to compare the lipid lowering efficacy
of international and local product of simvastatin in patients with
primary hyperlipidemia. Fifty patients with abnormal lipid profile were
included in the study (age 30-70 years). Patients were divided into two
groups (25 patients each). Group A was orally administered with
international product of simvastatin (10 mg)/day for 4 weeks and in group B, patients were
orally administered with local product of simvastatin (10 mg)/day for 4 weeks. Results: The
Cholesterol, Triglyceride (TG), High density lipoprotein (HDL) and Low density lipoprotein
(LDL) were estimated in the serum of patients before and after treatment with international
and local product of simvastatin (10mg/day). After the treatment serum Cholesterol,
Triglyceride and Low density lipoprotein were decreased in both groups, both drugs were
well tolerated by the subjects without any serious side effects. Conclusion: On the basis of
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Article Received on
26 May 2014,
Revised on 30 June
2014,
Accepted on 02 August 2014
*Correspondence for Author
Dr. Naveed Ali Siddiqui
Department of Biochemistry,
Bhitai Dental & Medical
College, Mirpurkhas, Pakistan.

this study we concluded that both international and local product of simvastatin are equally
effective.
Key words: Lipid profile, Hyperlipidemia, Local & International product, Simvastatin.
INTRODUCTION
Coronary heart disease is a leading cause of morbidity and mortality and high blood
cholesterol is a major risk factor for coronary heart disease [1-3]
. The incidence of coronary
heart disease in Pakistan is as high as in the Western world. According to National Health
Survey in Pakistan between 1990 and 1994, 13% of Pakistan adults were found to have
elevated blood cholesterol (random blood cholesterol >200 mg/dl). Coronary heart disease,
stroke, and vascular disease are the most common cause of adult mortality in the United State
[4-6]
. Once diagnosed, appropriate preventive measures include proper diet, regular exercise,
weight control and lipid lowering agents to reduce the risk of morbidity or death. In patients
with risk of coronary heart disease or with high levels of total cholesterol or LDL cholesterol,
drug therapy should be initiated at an early stage [7]
. Statins are considered to be the best drug
for treating individuals with elevated blood cholesterol levels [8,9]
. Statins (HMG-CoA
reductase inhibitors) are well established as lipid lowering agents used extensively in the
management of hyperlipidemia due to its high efficacy in reducing blood cholesterol levels
[10, 11, 12]
. It competitively inhibits HMG CoA reductase, the enzyme that catalyzes the rate
limiting step in cholesterol biosynthesis [13, 14, 15]
.
In Pakistan two types of simvastatin products are available. One is manufactured by
international companies and other is a local product, manufactured by Pakistani companies.
The international product is costly as compared to the local product. The physician and the
patients prefer to purchase the international products, but a lot of patients cannot afford to
purchase the costly products. So it was planned to assess the two products (international and
local) for their effectiveness in the treating hyperlipidemia.
MATERIAL AND METHODS
Patients Selection: The study was carried out at Surgeon Munawar Memorial Hospital
Bahadurabad, Karachi from year 2009 to 2011. The population under study was
representative of Pakistani population with primary hyperlipidemia. Blood pressure, body
weight and height of every subject were assessed. Blood pressure was measured using
mercury sphygmomanometer. The patient answered the questionnaire on health complaints,

smoking, social role, drug usage, family history and dietary pattern. Patients were asked to
fill a consent form before starting the experiment. The initial inclusion criteria of the patient
were 1) Age between 30 and 70 years old of either sex, 2) Patients with primary
hyperlipidemia, 3) No previous history of using any anti hyperlipidemic drugs. The exclusion
criteria were 1) Pregnancy or lactation, 2) Patients with liver diseases, 3) Patients with renal
diseases, 4) Patients with thyroid diseases, 5) Patients with established coronary artery
diseases or ischemic heart diseases. Detailed medical history and physical examination of all
patients were carried out.
Study Design: Fifty patients were selected for the study and divided into two groups (group
A and B). Each group was comprised of 25 patients. Twelve to fourteen hours fasting lipid
profile was done in both groups on the day of inclusion (day 0) before the treatment. Group A
was orally administered with the international product of simvastatin (10 mg/day) for 4
weeks and in group B patients received the local product of simvastatin (10 mg/day orally)
for the same duration. After a month blood samples were collected again for the estimation of
lipid profile.
Collection of Samples: The blood sample was drawn using 5ml syringe and centrifuged at
3000 rpm for 10 minutes. Serum was separated and collected in clean and dry Eppendorfs
and was stored at -70 C till further analysis.
Analysis of Serum Lipids: The serum levels of Total cholesterol, TG, and HDL were
determined enzymatically on microlab using commercially available (Randox laboratories
limited, UK) kits. LDL was calculated using Friedwald formula [16]
.
Statistical Analysis: The data was analyzed statistically using SPSS version [11]
.
RESULTS
Table no. 1 Age and Male to Female ratio in primary hyperlipidemia
In the present study 50 patients were investigated for the lipid lowering activity of the
international and local product of simvastatin. Table 1 shows the age of the patients and male
to female ratio which was 2.3:1.
Group Age (years) Males (years) Females (years) Ratio
Primary
hyperlipidemia
43.06
± 0.88
(50)
41.77
± 0.94
(35)
46.06
± 1.77
(15)
2.3 : 1

Table 2 represents the variation of serum lipids including Cholesterol, Triglyceride (TG),
High density lipoprotein (HDL) and Low density lipoprotein (LDL) in primary
hyperlipidemia before and after one month of treatment with international product of
Simvastatin (10 mg/day). The serum Cholesterol was decreased to 182.96±3.6 mg/dl while,
Triglyceride and Low density lipoprotein were also decreased after the treatment of
Simvastatin (10 mg/day) to the range of 161.32±2.16 mg/dl and 133.12±3.11 mg/dl
respectively. There were no significant changes observed in high density lipoproteins.
Table No. 2 Variation of Serum lipids in Primary hyperlipidemia before & after
treatment with international product of SIMVASTATIN
.
The values are given as Mean ± S.E.M and the number of cases are given in paranthesis.*p <
0.05 statistically significant as compared to the before treatment with international product of
SIMVASTATIN (10mg/day).
Table 3 represents the variation of lipid profile in patients with primary hyperlipidemia
before and after one month treatment with local product of Simvastatin (10 mg/day). Mean
serum Cholesterol levels changed from 189.96±3.41 mg/dl (before treatment) to 176.28±1.96
mg/dl (after treatment). Triglycerides were also lowered to 152.56±1.36 mg/dl in the same
manner. Low density lipoproteins were also found to be decreased after the treatment of
Simvastatin (10mg/day) from 143.56±2.78 mg/dl to 138.04±2.42 mg/dl.
Before
treatment
Cholesterol
mg/dl
TG
mg/dl
HDL
mg/dl
LDL
mg/dl
205.95
±7.14
(25)
186.00
±4.68
(25)
44.36
±1.32
(25)
136.88
±3.89
(25)
After
treatment
182.96*
±3.04
(25)
161.32*
±2.16
(25)
44.64
±1.10
(25)
133.12*
±3.11
(25)

Table No. 3 Variation of Serum lipids in Primary hyperlipidemia before & after
treatment with local product of SIMVASTATIN
Before
treatment
Cholesterol
mg/dl
TG
mg/dl
HDL
mg/dl
LDL
mg/dl
189.96
±3.41
(25)
170.40
±3.06
(25)
40.64
±1.10
(25)
143.56
±2.78
(25)
After
treatment
176.28*
±1.96
(25)
152.56*
±1.36
(25)
39.84
±0.75
(25)
138.04*
±2.42
(25)
The values are given as Mean ± S.E.M and the number of cases are given in paranthesis.*p <
0.05 statistically significant as compared to the before treatment with local product of
SIMVASTATIN (10mg/day).
DISCUSSION
Simvastatin is a lipid-lowering agent that is derived synthetically from the fermentation
product of Aspergillus terreus. Simvastatin is a white to off-white, nonhygroscopic,
crystalline powder that is practically insoluble in water, and freely soluble in chloroform,
methanol and ethanol. After oral ingestion, simvastatin, which is an inactive lactone, is
hydrolyzed to its corresponding (β)-hydroxyacid form [17]
. Hyperlipidemia or
hyperlipoproteinemia is the condition of abnormally elevated levels of lipids or lipoproteins
in the blood. According to World Health Organization (WHO), most of the lipids in plasma
are present as lipoproteins i.e. chylomicrons, very low density lipoproteins (VLDL), low
density lipoproteins (LDL), and high density lipoproteins (HDL). According to National
health survey in Pakistan between 1990 and 1994, 13% of Pakistani adults have elevated
blood cholesterol (random blood cholesterol > 200 mg/dl). Primary hyperlipidemia is
generally due to a single inherited gene defect or more commonly by combination of genetic
and environmental factors [18, 19]
.
The NCEP (national cholesterol education programme) recommends lowering LDL as the
primary target, followed by increasing HDL and lowering triglycerides. Statins are
considered as first-line therapy for the treatment of hyperlipidemia. This is an inhibitor of 3-
hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. This enzyme catalyzes the
conversion of HMG-CoA to mevalonate, which is rate-limiting step in the biosynthesis of
cholesterol. This increases the number of hepatic LDL receptors and enables more LDL to be

delivered to the liver. As a result, there is a reduction in the level of VLDL, LDL cholesterol
in the serum. In patients with hypercholesterolemia these action usually cause a decrease of
20-40% in serum LDL cholesterol levels and in increase of 10% in serum HDL cholesterol
levels [19]
.
HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitors are effective in
primary as well as secondary prevention of coronary disease. Therefore, these agents are used
as the first choice for hypercholesterolemia in this subset of the population, especially
Simvastatin [20]
.
Simvastitin decreases concentrations of total cholesterol (p < 0.001), low-density lipoprotein
cholesterol (p < 0.001). It also reduces the concentration of triglycerides [11, 23, 24]
. In the
present study effects of international and local product of Simvastatin were assessed on
primary hyperlipidemic patients. The mean age of the patients was 43 with a male: female
ratio of 2.3:1 (Table 1). These individuals were treated with international and local product of
simvastatin as cases of primary hyperlipidemia, their serum cholesterol, triglyceride and low
density lipoprotein (LDL) were significantly decreased (p < 0.05) after treatment (Table 2, 3).
In the present study cholesterol levels were decreased by 23mg/dl and 13mg/dl (difference of
before and after treatment from 205 mg/dl to 182 mg/dl and 189 mg/dl to 176 mg/dl) while
TG were decreased by 25 mg/dl and 18 mg/dl (difference of before and after treatment) after
using international and local product of simvastain respectively, our study matches with the
study of Antti Jula [25]
.
High LDL levels and low concentration of HDL plays an important role in the generation of
cardiovascular diseases, statins therefore target the increased LDL cholesterol levels [26]
. In
our study LDL levels were found to be decreased after the treatment of simvastatin products
(from 136.88 mg/dl to 131.12 mg/dl by the action of international product and from 143.56
mg/dl to 138.04 mg/dl after treating with the local product).
It was observed that international and local product of Simvastatin were well tolerated and
effective as cholesterol lowering agent with a good safety profile in primary hyperlipidemic
patients. No laboratory evidence of adverse reactions was observed.
High blood levels of cholesterol play a leading role in atherosclerotic lesion formation in the
walls of coronary arteries. Over time fatty lesion progress to fibrous plaque. Fissures may

develop in a plaque, exposing the underlying tissues to platelets and other constituents of
blood. Platelets adhesion, activation, aggregation lead to thrombus (clot) formation, partially
or completely occluding the vessel lumen and causing ischemia leading to myocardial
infarction [21, 22]
, this may be prevented by the statin therapy and our study suggests that both
international and the local products of simvastatins are equally effective in patients with
primary hyperlipidemia.
CONCLUSION
These comparative studies showed that both international and local product of Simvastatin
are equally effective. Simvastatin is the drug which prevents development of atherosclerosis
and evident myocardial infarction that is one of the major causes of sudden death in Pakistan.
Since the local product is equally effective as the international brand. The difference of price
range makes local product more affordable to the Pakistani population. Due to the rising cost
of imported drugs, one strategy of the National Drug Policy is to promote the usage of locally
made generic products. The local manufacturing of medicines like simivastatin should be
strongly encouraged, provided it can give equivalent safety and efficacy to the original
product.
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