Print ISSN: 1680-2594

Online ISSN: 2264-2522

Volume 11, Issue 2

Volume 11, Issue 2, Autumn 2011, Page 1-114


Synthesis and in vitro kinetic study of novel mutual azo prodrug for inflammatory bowel disease

Yasser Fakri Mustafa

Iraqi Journal of Pharmacy, Volume 11, Issue 2, Pages 1-11

Background: Inflammatory bowel disease (IBD) refers to idiopathic inflammatory
diseases of the intestine, principally ulcerative colitis and Crohn’s disease. IBD is
characterized by chronic inflammation in the mucosal membrane of large intestine. 5-
ASA is the gold standard for the treatment of IBD and when searched for a better 5-
ASA prodrug, a novel mutual azo prodrug was designed and synthesized.
Methods: A mutual prodrug was synthesized by coupling p-phenetidine with
salicylic acid. The stability of this prodrug in HCl buffer, in phosphate buffer and in
rat fecal matter were monitored.
Results: The chemical structure of mutual prodrug was characterized by physical and
spectroscopic techniques using FTIR, UV/Visible, 1H-NMR and 13C-NMR spectra. In
vitro kinetic studies in HCl buffer (pH 1.2) showed negligible release of 5-ASA and
p-phenetidine, whereas in phosphate buffer (pH 7.4) only (22.04 %) release was
observed over a period of (6 hr.). In rat fecal matter, the hydrolysis of mutual prodrug
was almost complete (77.96 %), with a half-life of 182.67 min, following zero order
kinetics.
Conclusion: The mutual prodrug was split in colon by the action of bacterial
azoreductase into 5-ASA and p-phenetidine that constitute two anti-inflammatory
compounds with different mechanisms of action. Therefore, this mutual prodrug is a
promising colon specific prodrug for IBD and worthy of further study.

Assessment of serum carcinoembryonic antigen in colorectal cancer patients treated by surgery and chemotherapy

Shahbaa A. Al-Bayati

Iraqi Journal of Pharmacy, Volume 11, Issue 2, Pages 12-16

Objective: Carcinoembryonic antigen (CEA) is a protein found in many types of cells
associated with tumors and the developing fetus. The main use of CEA is as a tumor
marker, especially with intestinal cancer. This study was designed to evaluate the
effect of surgery and chemotherapy on the level of CEA.
Patients and methods: The study was carried out in Al-Jamhoory Teaching Hospital
in Mosul from January to July 2010. Thirty patients with colorectal carcinoma were
treated by surgical removal of the cancer and chemotherapy. Blood samples were
taken from the patients one week before surgery and other blood samples were taken
one week after surgery. Third blood samples were taken after one week of the first
cycle of chemotherapy. Serum carcinoembryonic antigen, ALP (alkaline
phosphatase), ALT (alanine aminotransferase), total serum bilirubin (TSB), and
albumin were estimated from the samples.
Results: After surgery serum CEA and WBCs were decreased significantly (P <
0.001). Serum ALP was also decreased significantly (P < 0.05), while serum ALT,
TSB, and albumin were not changed significantly after surgery compared with the
results before surgery. After chemotherapy, serum CEA and WBCs decreased
significantly (P < 0.001) compared with the results after surgery. At the same time,
serum ALP, ALT, TSB, and albumin did not change significantly after chemotherapy.
Conclusion: Surgical removal of tumor decreased CEA level, but it did not
normalize. Serum CEA can be used as a marker for the effectiveness of the
chemotherapy on colorectal cancer.

Preparation of modified release diltiazem HCl capsule by complexation with ion exchange resin

Eman B.H. Al-Khedairy; Alaa A. Abdulrasso; Jenan M. AL-Mosawi

Iraqi Journal of Pharmacy, Volume 11, Issue 2, Pages 17-26

Background: Diltiazem HCl is a calcium channel blocker drug used in the treatment
of angina pectoris and hypertension.
Objective: To prepare a sustained release diltiazem HCl capsule by complexation
with polystyrene sulfonate strong cation exchange resin (dowex®50wx4) as a
complexing and retarding agent.
Methods: The effect of stirring time and drug: resin ratio on diltiazem HCl loading on
dowex®50wx4 was studied. Drug resin complexes were characterized by Fourier
Transform Infrared (FT-IR) spectroscopy. The release of drug from the complexes
was examined in pH 1.2 and pH 6.8 separately in comparison with pure drug and with
commercially available sustained release products Tildia® 120mg capsule and BITildiem
® 120mg tablets
Results and conclusion: Most efficient loading was obtained using 1:2 and 1:2.5
drug:resin ratio with stirring time of 60 and 30 minutes respectively. The resultant
complexes only retard the release of diltiazem HCl when compared with pure drug
while the sustained release product was obtained by coating the complex with
carnauba wax and the retardation increased as a function of wax concentration. 20%
of wax coated complex gave the release profile approximately similar to the marketed
sustained release product of diltiazem HCl, Bi-Tildiem® (Sanofi-France) 120 mg
tablets.

The effect of antioxidant supplementation in the treatment of epilepsy

Nazar A.K. hamid

Iraqi Journal of Pharmacy, Volume 11, Issue 2, Pages 27-33

Aim: To assess serum level of malondialdehyde (MDA) and total antioxidant status
(TAS) as a representative of oxidative stress in patients with generalized epilepsy and
to evaluate the therapeutic effect of the antioxidant (vitamin E and vitamin C) on the
levels of MDA,TAS and frequency of seizures attacks after two months therapy. for a
period of two months as a supplementation therapy.
Subjects and Methods: The study was conducted in Iben-seena Hospital in Mosul
city-Iraq. Fifty three patients with generalized epilepsy were included in this study
(32 male and 21 female). The study included 40 apparently healthy subjects, age and
sex matched as a control group. Initially from both the patients and controls, blood
samples were taken. Another blood samples were taken from the patients 2 months
after vitamin E and vitamin C treatment, blood samples were analysed for serum
MDA and serum TAS.
Result: Serum MDA was found to be significantly higher ( P<0.001) and serum TSA
was significantly lower (P<0.001) in patients with generalized epilepsy prior vitamin
E and vitamin C supplementation in comparison to controls. After vitamin E and C
supplementation there was a significant reduction (P<0.001) in the serum MDA levels
with a significant increase (P<0.001) in the serum TAS. Also we found a reduction in
seizure frequency of greater than 70% after vitamin E and C supplementation.
Conclusion: a significant reduction of TSA was reported in patients with epilepsy.
Administration of vitamin E and C produced a significant reduction of serum MAD
levels and a significant elevation of serum TAS, associated with a reduction of greater
than 70% of seizure frequency. The study suggests the administration of vitamin E
and C as adjunct to antiepileptic drugs.

The effect of rifampicin and isoniazid on liver and lung tissues in rats

Dalal F. Ahmed

Iraqi Journal of Pharmacy, Volume 11, Issue 2, Pages 34-45

Objectives: The purpose of this study was to investigate the histopathological
changes in Swiss albino rats liver and lung tissues resulted from the oral
administration of the antituberculous drugs rifampicin and isoniazid.
Materials and Methods: The study was conducted on 24 adult rats aged 2.5-3
months weighing 200-250 g randomly distributed into four groups(6 animals for
each), the first group served as a control group while the remaining three as test
groups. The rifampicin group was treated with 50 mg/kg B.W. once per day for 60
days, the isoniazid group was treated with 25 mg/kg B.W. once per day for 60 days,
the rifampicin and isoniazid groups were treated with 50, 25 mg/kg B.W. respectively
once per day for 60 days.
Results: Giving rifampicin alone orally once daily for 60 days caused fatty
degenerative and necrotic changes in the liver in addition to proliferative lesions and
emphysema in the lung. Rats receiving isoniazid alone orally once daily for 60 days
showed similar degenerative and necrotic changes in liver and lung but of lower
intensity. Whereas those receiving rifampicin and isoniazid combination for 60 days
showed pathological changes similar to those induced when each of the two types of
antituberculosis drugs was given alone but of more intensity.
Conclusion: Rifampicin and isoniazid showed clear histopathological changes in the
rat's liver and lung tissues when given separately ; however, changes where more
intense when givenin combination.

Effects of estrogen replacement therapy on symptoms and clinical parameters in post menopausal women

Norjihan Ali Shaban; Kawa Dizaye

Iraqi Journal of Pharmacy, Volume 11, Issue 2, Pages 46-57

Objective: To evaluate the effect of oral estrogen replacement therapy (ERT) in healthy
postmenopausal women on lipid profile, body mass index (BMI), blood pressure, and
blood glucose; and on postmenopausal symptoms.
Subjects and Methods: This prospective cohort research was carried out over a period
of eight months, from Jun 2007 to February of 2008. Fifty six postmenopausal women
(mean SD age of 53.3±3 years; mean menopausal period, 5 years); previously diagnosed
by gynecologist were involved in this study. Thirty six postmenopausal women were
treated with oral conjugated equine estrogen (CEE) (premarin®) 0.625 mg daily for two
months. Twenty postmenopausal women were served as control and received daily dose
of placebo.
Results: In postmenopausal women treated with conjugated equine estrogen, serum total
cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were decreased
significantly as compared with placebo, while there was no significant change in the
serum level of high-density lipoprotein cholesterol(HDL-c). In both groups, estrogen
induced changes in plasma triglyceride and reduced the size of LDL particles. These
observations suggest that the plasma TG increase may reduce the size of LDL particle.
CEE lowered blood pressure, decreased fasting blood sugar and increased BMI of
postmenopausal women . Significant positive correlation was found between the BMI
and total blood cholesterol whereas significantly negative correlation was found between
the BMI and LDL of treated postmenopausal women. CEE effectively alleviated
bothersome symptoms of postmenopausal women such as hot flushes, night sweat and
vaginal dryness. Whereas, it has no detectable effects in attenuating bone pain.
Conclusion: CEE causes change in lipid profile, BMI, blood pressure and attenuates
bothersome symptoms in postmenopausal women.

Synthesis of new metoclopramide derivatives and in vitro evaluation of their human cholinesterases protection against Chlorpyrifos

Islam Tarik Qasim; Ahmed A.J. Mahmood; Yasser Fakri Mustafa

Iraqi Journal of Pharmacy, Volume 11, Issue 2, Pages 58-69

Objective: The purpose of this study was to synthesize three new derivatives of
metoclopramide by diazotization and replacement reactions and then to quantify in
vitro their protection effects on blood cholinesterases using chlorpyrifos as a potent
inhibitor.
methods: The three new metoclopramide derivatives were synthesized via
Sandmeyer reaction, the chemical structures of these derivatives were identified by
physico-chemical and spectroscopic (U.V. and FTIR) techniques.
Results and conclusion: The results of in vitro evaluation of their human
cholinesterases inhibition and protection against chlorpyrifos indicated that the (OH)
functional group binds to cholinesterase (ChE) at the same organophosphorous (OP)
binding site and shows some competition and protection ability but not to a significant
degree, while the (Cl and I) functional groups bind to the ChE at site differs from OP
binding site, as well as the (I) functional group has more selectivity for enzyme
moiety and binds more strongly than the (Cl) group, so that shows more ChE
inhibiting ability

Cerebrospinal fluid cholinesterase activity in children with meningitis

Aldeen Alnoori; Mohammed Khalid Jamal

Iraqi Journal of Pharmacy, Volume 11, Issue 2, Pages 70-76

Objective: To assess the changes of cerebrospinal fluid (CSF) acetyl cholinesterase
(AChE) activity in children with acute bacterial meningitis in comparison to healthy
age and sex matched controls.
Patients and methods: Out of 41 cases admitted to Alkhansaa pediatric and dilivery
hospital (Mosul city) between January 2010 and July 2010, 28 cases proved to be a
case of Haemophilus influenzae meningitis, 13 child proved lack from any type of
meningitis with age and sex matched subjects taken as a control group. Initially from
all of the studied children (patients and controls) about 5 ml CSF samples were taken
and assayed for appearance, leucocytes, red blood cells, sugar, protein and AChE
activities by spectrophotometric method.
Results: There were a significant increase in CSF WBCs count, RBCs count, protein
levels, AChE activity with a decrease in CSF glucose level for children with acute
bacterial meningitis in comparison to the control group.
Conclusion: There is an important value for measurement of CSF AChE activity for
confidential diagnosis of children with acute bacterial meningitis specially for those
with equivocal decision by using the traditional parameters.

Indirect spectrophotometric method for the determination of bisacodyl in commercial dosage forms and in environmental water samples

Nawal A. Majid; Nief Rahman Ahmad

Iraqi Journal of Pharmacy, Volume 11, Issue 2, Pages 77-84

Objective: A simple, sensitive, and accurate indirect spectrophotometric method for
the determination of bisacodyl in pure form and in some of its pharmaceutical
preparations.
Method: The method is based on the oxidation of bisacodyl by iron (III), and
subsequent complexation of iron (II) with o-phenanthroline.
Results: Forming a red-colored complex (ferroin) having the maximum absorbance at
510 nm. Beer’s law is obeyed in the concentration range of 0.5-5 µg/ml. The molar
absorptivity and sandell’s sensitivity were 1.55×104 L.mol-1.cm-1 and 0.0233µg.cm-2
respectively. The relative standard deviation (RSD) was less than 1.5 (n=11). The
limits of detection and quantitation are 0.083 and 0.25 µg.ml-1 respectively.
Conclusion: The method is applied successfully for determination of bisacodyl in
environmental water samples and in some pharmaceutical formulations (tablets and
suppositories). A statistical comparison of these results with those of official method
shows good agreement and indicates no significant difference in the precision.

Detection of Toxoplasma gondii IgM and Cytomegalovirus IgM antibodies among blood donors in Mosul

Karam A. Al-Dabbagh

Iraqi Journal of Pharmacy, Volume 11, Issue 2, Pages 85-92

Background: Toxoplasmosis is an infection caused by the protozoan parasite
Toxoplasma gondii. This parasite can be transmitted via blood transfusion.
Cytomegalovirus (CMV) is a herpes virus that can cause many complications and
mostly transfer via blood transfusion. The aim of this study was to evaluate the
percentage of risk of infections that could occur due to blood transfusion.
Subjects and methods: Ninety blood donor samples were randomly obtained from
central blood bank of Mosul city and investigated for IgM of toxoplasmosis and CMV
by the serological method ELISA, IgM.
Results: ELISA test for Toxoplasma gondii IgM test showed 3% seropositive and for
CMV showed 10% seropositive.
Conclusion: The results indicate a risk of infection with toxoplasmosis and CMV via
blood transfusion.

In vitro kinetic study of donepezil N- oxide metabolites

Faris T. Abachi; Ammar B. Behnan; Riyath A. Atto

Iraqi Journal of Pharmacy, Volume 11, Issue 2, Pages 93-101

Objective: The aim of this study was to examine the metabolism of donepezil via N
– oxidation of donepezil HCl in vitro, and the kinetic studies at a temperature similar
to that of the human body.
Methods: Direct reaction of donepezil with hydrogen peroxide and formic acid at
room temperature, the N – oxide undergoes a series of rearrangements, the reaction
was followed by ultraviolet at λmax= 268 nm at 37 °C. The donepezil N- oxide was
also tested as potential cholinesterase inhibitor using electrometric for cholinesterase
determination.
Results: According to the present work , the structure of donepzil N- oxide was
elucidated using spectroscopic analysis , also , in vitro kinetic study at 37 °C using
ultraviolet spectrophotometer at λmax = 268 nm showed that the reaction proceeded at
a first order reaction . Biologically, the compound was found to inhibit both plasma
and erythrocyte cholinesterase activities in vitro ..
Conclusion: We concluded that the N- oxide of denepezil undergoes a series of
rearrangements, the reaction followed first order at 37 °C. It has a potential
anticholinesterase activity

Comparison between quantitative and qualitative biochemical markers in the diagnosis of acute coronary syndrome

Akram J Ahmad; Samir B Al-Mukhtar

Iraqi Journal of Pharmacy, Volume 11, Issue 2, Pages 102-110

Objectives: To compare between the qualitative estimation of biochemical markers
Point-of-Care testing) with the quantitative estimation of the same markers in the
diagnosis of acute coronary syndrome (ACS).
Design: Case-series study.
Setting: This study was carried out in coronary care unit in Ibn- Sena Teaching
Hospital in Mosul city from January to November, 2008.
Participant: Sixty five patients with acute coronary syndrome (ACS) presented with
chest pain.
Main outcome measures: Three cardiac markers (Creatine kinase (CK-MB)
activities (marker of necrosis), myoglobin (marker of muscle injury), and troponin I
(marker of necrosis), were estimated qualitatively (near the patient= Point-of-Care
testing), and quantitatively, and the results were compared. Kappa test was used for
the association between the quantitative and qualitative test results.
Results: The case-series study showed correlation of attributes between qualitative
estimation results of troponin I, myoglobin and CK-MB and quantitative estimation
results of the same parameters in (88.9%) tests.
Conclusion: The early diagnosis of ACS might be facilitated by the use of qualitative
point-of-care testing based on CK-MB, troponin I and myoglobin tests.

Serum immunoglobulin levels in male schizophrenic patients before and after olanzapine therapy

Mahmoud Khudhayer Oglah Hussein

Iraqi Journal of Pharmacy, Volume 11, Issue 2, Pages 111-114

Objective: To evaluate the effect of olanzapine therapy on serum immunoglobulin
levels (IgA, IgG, IgM) in male schizophrenic patients after 2 months of treatment by
olanzapine at a daily dose of 20 mg.
Patients and Methods: Twenty-eight patients with schizophrenia were included in
this study, assessment of each case was done by a psychiatric, also included a 30
healthy subjects as a control group. Serum immunoglobulin concentrations were
determined for both patients and controls by Mancini Radial Immuno-diffusion
method using immunoglobulin kits. For the patients group and after 2 months therapy
with olanzapine at a fixed daily dose of 20 mg, serum immunoglobulins were
determined again using the same method for the assay.
Results: No significant difference was found between serum levels of
immunoglobulin (IgA, IgG, IgM) in schizophrenic patients before therapy in
comparison to controls. Also insignificant difference was found between serum
immunoglobulin levels (IgA, IgG, IgM) in schizophrenic patients after 2 months of
olanzapine therapy and the controls. By comparing serum immunoglobulin levels in
patients with schizophrenia before and 2 months after starting olanzapine therapy, no
statistically significant difference was found.
Conclusion: Olanzapine as atypical antipsychotic may not have an influence on the
humoral immune response as reflected by the immunoglobulin levels (IgA, IgG, IgM)