فهرست مطالب mohammadreza shiran

Alzheimer’s disease (AD) is a neurodegenerative condition characterized by a gradual onset and progressive deterioration. Recent studies have demonstrated that certain antihyperglycemic drugs can slow down the progression of AD.

This study aimed to investigate the effects of sitagliptin (SG) and metformin (MTF) on scopolamine (SCP)-induced learning and memory impairment in both diabetic and non-diabetic mice.

This experimental study was conducted with two subgroups of mice, one diabetic and one non-diabetic. Over a 14-day period, the animals received different doses of SG and MTF in addition to a combination of these two drugs. On the 14th day, SCP was administered, followed by a memory impairment test (passive avoidance learning) conducted 45 minutes later. Subsequently, the animals were sacrificed, and brain samples were collected to measure oxidative stress biomarkers, including malondialdehyde (MDA), glutathione (GSH), glutathione peroxidase (GPx), catalase (CAT), and superoxide dismutase (SOD).

The obtained findings revealed that intraperitoneal injection of SCP impaired learning and memory function and caused brain oxidativedamagein both diabeticand healthy mice. In healthy mice, the administration of high doses of MTF(500 mg/kg) and SG (20 mg/kg), in addition to the combination of these two drugs, significantly reduced memory impairment and oxidative stress. However, in the diabetic groups, only MTF and the combination of MTF with SG could reduce memory impairment and oxidative stress.

The authors concluded that these antidiabetic drugs ameliorated oxidative stress by increasing antioxidant capacity and improved scopolamine-induced memory impairment. Furthermore, the combination of these two drugs yielded more favorable results.

Production of functional foods is one of the most important achievements in food industry and using these products provides the convergence of two important events in life; namely receiving nutrients from the diet and promoting health for consumers at the same time. This study aimed to verify the viability of microorganisms and stability of these microorganisms in digestive conditions of the body in order to benefit from the claimed properties of these products.

In this experimental study, 14 samples of probiotic yogurts were collected from three dairy factories in Mazandaran province in summer 2020. The test method consisted of three main steps; determining the viability of probiotic bacteria in the samples over time, then simulating the conditions of the gastrointestinal conditions, including pH changes and exposure to pepsin and bile salts, and finally, evaluating the resistance of microorganisms after passing the conditions of gastric and intestinal simulated condition. Statistical analysis was performed using SPSS.

In the study of viability of Bifidobacterium and Lactobacillus, a significant difference was observed between the mean number of colonies both at different weeks and different pH levels (P<0.05). Yet, the number of probiotic bacteria remained within acceptable standard range (106 cfu/g) over time and did not show a considerable reduction even after passing the acidic and alkaline conditions and tolerating the simulated digestive conditions.

According to this study, if strains (probiotic bacteria) resistant to acid and bile are selected and also suitable environmental conditions are used, consumption of probiotic yogurts can be of great benefit in improving the health of consumers.

In this study, Alyssum homolocarpum (AH) and Lepidium sativum seed gum (LS) at different ratios 1:0, 1:1, and 0:1 utilized to encapsulate red onion extract (ROE) for beef coating through immersion. Different concentrations of ROE (400, 800, 1200 and 1600 ppm) showed high antioxidant activity due to phenolic and flavonoid compounds. In terms of mean size, the lowest particle size was observed in ROE encapsulated in Alyssum homolocarpum gum (7.4 3 89.3 nm). And nanoemulsions prepared in Lepidium sativum seed gum had higher particle size (145.7 3 2.3 nm). Negative-zeta potential was observed in all nanoemulsions. Meat samples were kept at 4 ° C for 20 days and the values ​​of thiobarbituric acid, color indices L *, a *, b *, total bacterial count were examined at 4-day intervals. The results showed that ROE encapsulated in LS and AH was more effective in delaying the microbial and chemical reactions of coated meat fillets. Due to reduced bacterial growth, decreased thiobarbituric number and microbial growth, shelf life increased from 4 days to 16 days. This study confirmed that ROE encapsulated in the combined coating of AH and LS is a potential coating to improve the quality and shelf life of beef fillets.

Sumatriptan is a routine medication in the treatment of migraine and cluster headache that is generally given by oral or parental routes. However, a substantial proportion of patients suffer severe side effects. The aim of this study was to investigate the physicochemical characterization and pharmacokinetic parameters of a novel delivery system for sumatriptan succinate (SS) using nanoliposomes (NLs) coated by chitosan (CCLs) to optimize the formulations to enhance its bioavailability.

The new formulation was used to minimize drug particle size and extend its release and bioavailability. The mean particle size and entrapment efficiency for NLs and CCls were optimized and the formulations with better characteristics were chosen for in vivo studies. The concentration-time profile of intravenous SS, intranasal SS, SS-NLs, and CCLs were examined in a rabbit model.

The results demonstrated that CCLs were absorbed more rapidly from nasal drops containing chitosan compared to those of SS and SS-NLs as indicated by a shorter tmax, and a higher Cmax in both states. A comparison of the AUC (0-240 min) values revealed that chitosan improved the extent of SS absorption for CCLs formulation. The results of the present study indicated that loading SS into the liposome and coating with chitosan improves drug absorption and a large amount of the drug can be efficiently delivered into the systemic circulation.

The liposomal and chitosan formulations of SS had better kinetic behavior than the soluble form in the animal model.

Extensive use of various forms of medicinal plants makes it necessary to continuously monitor the production and supply of these plants. Also, it is important to study metal and pesticide contaminants in medicinal plants in order to prevent hazards from their consumption. This study aimed at investigating the pollutants and mineral element levels in widely consumed medicinal plants in Mazandaran province, Iran.

In this descriptive study, 19 plant samples, including Melissa officinalis, Mentha piperita, Echium amoenum, Lippia citriodora, Rosa damascena, etc. were collected from four medicinal plant farms in Behshahr, Sari, Babol, and Baladeh Noor in Mazandaran province in spring and summer of 2020. Measurement of elements in plant samples was performed using induction coupled plasma device (ICP) and Determination of agricultural pesticide residues was carried out using GC/MS.

Among the samples examined, residues of agricultural pesticides were not detected in any samples. Different levels of heavy metals and essential elements in the same species of plants could be due to various factors, including water, soil, and air pollution. The highest amount of lead was observed in lemon beebrush (5.938 ppm) in Behshahr and peppermint (4.4 31 ppm) in Babol. The highest amount of cadmium was detected in stevia collected (0.291 ppm) from Sari.

Despite the relative lack of risk of samples studied, different forms of medicinal plants should be used with caution. Medicinal plant farms also need to be regularly monitored and precautions must be taken to control heavy metal contamination in plant-based foods.

 Drug allergy is a subtype of Adverse Drug Reactions (ADR) mediated by the immunologic system. Extreme drug allergy is poorly known in children that contribute to the hospitalization in our region.

 This research aimed to study major drug hypersensitivity reactions in the north of Iran among hospitalized children.

 This corss-sectional study conducted at the Bou Ali Sina hospital, north of Iran, analyzing the medical history of 140 children with drug allergies from 2014 to 2018. Inclusion criteria were based on the DRESS scoring system, and those who scored more than four were enrolled. Patients with incomplete medical charts were excluded. The sampling methodology was based on the consecutive census.

 In the current study, 62 patients were females (44.29%), and 78 were males (55.71%). Ninety-six cases (68.57%) were children under five, and 44 cases (31.43%) were over five years old. Most ADRs were seen in patients from urban areas (58.57%)  than in rural areas (41.43%). In 82.6% (116 children) of these patients, maculopapular rashes were seen. Phenobarbital and cefalexin had the highest levels of drug reactions, including 55.19% of patients (85 persons) and 11.69% of patients (18 persons), respectively. Pruritus, fever, and scaling were the most common symptoms observed in patients. The most commonly used treatment was antihistamines.

 The most causative medication inducing ADR was phenobarbital. The maculopapular rash was the most common skin manifestation, and there were no relationship between sex, age, medication type, and type of hypersensitivity reactions.

Global prevalence of neurological disorders such as Parkinsonchr('39')s disease, Alzheimerchr('39')s disease, epilepsy, and multiple sclerosis is steadily increasing, but, there is still no effective delivery system to deliver therapeutic amounts of drug into the central nervous system (CNS). The blood-brain barrier ​​is the major component to control the entrance of drugs into the brain. Recent studies introduced intranasal drug delivery as a suitable method of drug delivery for bypassing blood-brain barrier and treatment of neurological diseases. The nasal route has been repeatedly examined in several preclinical models to investigate the delivery of drug to the brain via nanoparticles. Among various carriers utilized for drug delivery via nasal route, chitosan is widely used due to being effective in modulating drug charge. Key features of drug delivery systems through nasal route include easy drug delivery, higher stability in nasal cavity, increased penetration ability of drugs through nasal epithelium, and decreased drug metabolism. The present review investigated novel nano-formulations for drug delivery via nose to brain in treatment of major neurological disorders. In preclinical studies, intransaal nanoparticle-based drug delivery systems are found to be more promising, effective, and targeted. However, more preclinical studies are needed to confirm their non-toxicity and beneficial effects.

Sumatriptan is a routine medication in the treatment of migraine and cluster headache that is generally given by oral or parental routes. However, a substantial proportion of patients suffer severe side effects. Nasal administration is significantly effective in case of oral administration of drug gives an undesirable side effect. So, the purpose of the present study was to develop intranasal delivery systems of Sumatriptan succinate using nanoliposomes as container of a water-soluble drug and chitosan as a mucoadhesive polymer.

Liposomal formulations containing Sumatriptan as well as chitosan-coated liposomal formulations with different phospholipids and different concentrations were prepared. The formulations were evaluated for their physicochemical properties, stability and Cytotoxicity on BEAS-2B cells.

The prepared liposomal formulations coated with chitosan containing Sumatriptan had a size range of 165±9.4to 258±6.4 nm, and the surface charge of the obtained formulations was measured between 32±6 and 40±5 mV. Also, the encapsulation efficiency of the formulations was also observed between 14.2±2.7% and 19±3.4%. Based on the obtained results of physicochemical studies, liposomes F2 was also tested for stability and toxicity and showed that the F2 liposomes retained its physicochemical properties for up to 3 months. Finally, the toxicity test of the mentioned formulation showed relatively low toxicity on BEAS-2B cells.

In the presents study, stable liposomal formulations coated with chitosan containing Sumatriptan were prepared and studied. Based on the obtained, these formulations can be used in preclinical and animal studies for the nasal administration of Sumatriptan.

The antioxidant and anti-inflammatory properties of tarragon make it known as an antidiabetic plant. Diabetes mellitus, an endocrine, metabolic disease, is a leading global health emergency and associated with serious complications.

This study aimed to assess the effects of tarragon powder supplementation on glucose metabolism, lipid profile, and antioxidant status in the diabetic population.

Patient screening and selection for this clinical trial lasted one month. Tarragon supplement consumption by patients lasted 2 months (8 weeks); meanwhile, they were followed up. Sixty male and female patients with type 2 diabetes were randomly assigned to the tarragon receiver group (n = 30) and placebo receiver group (n = 30). The intervention group received a tarragon capsule (500 mg) 3 times a day, and the control group received placebo capsules. Fasting blood glucose (FBG), two-hour postprandial glucose (2-hpp), glycated hemoglobin (HbA1c), insulin, lipid, and antioxidant profile were evaluated at the start and the end of the research.

In the tarragon receiver group, FBG, 2-hpp, HbA1c%, insulin resistance, lipid, and antioxidant profile significantly improved, compared to the placebo group, after adjuvant therapy with tarragon (P < 0.05).

Supplementation with tarragon powder in type II patients with diabetes for 2 months exerts a beneficial effect on improving the glycemic profile, lipid profile, and antioxidant status.

Waste accumulation has very negative impacts on human health and the environment, but if managed properly, it can help in increasing food safety of the community. Agricultural extension and education as one of the main pillars of modern agriculture can play an effective role in agricultural productivity and waste and in general improve the living conditions of farmers. The purpose of this study was to investigate the role of education on rice waste management in Sari, Iran with emphasis on environmental protection and health.

This structural equation-based correlational survey was performed in 290 rice cultivators in Sari, north of Iran. The participants were selected based on Cochranchr('39')s formula. Data were collected using a researcher-made questionnaire. Based on the average variance extracted (0.506 >AVE< 0.581) and composite reliability (0.946 >CR < 0.953), the questionnaire had convergent validity and appropriate reliability. SPSS V16 and SmartPLS 2.0.M3 were used to analyze the data.

The study showed that trainings on the use of straw and other residues of rice positively affects rice waste management operations and is linked to environmental protection and better health status.

Without knowledge of rice waste management operations and proper trainings, rice cultivators cannot be expected to succeed in waste management while considering environmental protection and health.

Labelling is a communication tool between the manufacturer/ distributor and customer which includes all optional and mandatory information about a product. Awareness and education are the primary steps in forming a positive attitude toward food labels. The purpose of this study was structural equation modeling in awareness and attitude of consumers about food labels in Sari, north of Iran.

This survey research was performed in 2019. The research population included all food consumers in Sari, of whom 167 were selected as the study sample based on Cochranchr('39')s formula.  Data were collected using a researcher-made questionnaire. According to the average variance extracted (0.501 >AVE< 0.621) and composite reliability (0.823 >CR < 0.941), the questionnaire had a convergent validity and appropriate reliability. SPSS V16 and SmartPLS 2.0.M3 were used to analyze the data.

The study showed that characteristics of the products and food labels, and consumer’s age, and educational level had significant effects on their awareness of food labeling (P<0.01). The awareness of the consumers about food labels and consumer’s age were found to significantly influence their attitude toward food labels (P<0.01).

Efforts should be done to increase consumers awareness about food labeling which consequently improves their ability to interpret food labels and their attitude towards food labels.

Today, the tendency to use biodegradable biopolymers as one of the appropriate technologies to prevent food oxidation has received much attention.

The aim of the present study was to produce a new biodegradable films containing free ethanolic extracts and nanocapsules of kak kosh biabani (Pulicaria gnaphalodes (Vent.) Boiss.), in order to investigate the antioxidant properties in laboratory conditions.

In this study, the effects of different films on mechanical properties, antioxidant activities, encapsulation efficiency, water vapor permeability, microstructure and morphology and color characteristics were evaluated.

The average particle size was 153-166 nm and the encapsulation efficiency was 49.87-73.07%. Nanoliposomes with the lowest size and highest encapsulation efficiency were merged with the film samples. The results obtained from FT-IR spectra revealed new interactions between chitosan and nanoliposomes. Despite the increase in yellow color and decrease in whiteness indices, the nanoliposome composition improves the mechanical stiffness and results in reduced water vapor permeability (WVP).

The properties of chitosan-zein films were affected by the amount of extract used, which generally improved the properties of the films and their antioxidant properties. Due to these features, this film can be used in food storage.

All organisms struggle to survive and find food. This is the biggest and most important need of all organisms. Meanwhile, food safety is very important. Nanotechnology has penetrated every aspect of human life and plays an important role in the food industry. This technology has changed production and services as well as packaging and specifying the expiration of the food. Metal and metal oxide nanoparticles, chitosan, polymeric nanoparticles, and liposome are the most common particles in the packing and food protection. Here is a review of a number of developments in the nanotechnology over the food industry.

This study was a Nonsystematic Review and was searched through the databases Pubmed, SCOPUS, Web of Science, and Google Scholar with the keywords Nanotechnology, Nanoparticle, Packaging, and Food Science in recent years (2015-2018). There were 852 articles of which 43 papers were selected.

Metal and metal oxide nanoparticles, chitosan nanoparticles, polymer nanoparticles, and liposomes are the most commonly used particles in packaging and food preservation. The use of various nanoparticles and nanoparticle-coated composites, nanofilms, etc. has improved the quality and shelf-life of foodstuffs.

Nanotechnology has been able to influence the food industry as an emerging technology that has entered into all aspects of human life.

Propranolol is the most widely used treatment for cardiovascular diseases. Dosage range in our patients is usually less than the amount mentioned in references. The aim of the present study was to clarify whether pharmacokinetic differences are able to justify the need for the fewer doses in our patients or not.
Twenty healthy volunteers (10 male) at heart center of Mazandaran University of Medical Sciences were studied. Samples of blood were collected before a single oral dose (40 mg) of Propranolol. Blood samples were taken up to 9 hours after dose. Total plasma concentration of Propranolol was measured by HPLC. Population Pharmacokinetic analysis was performed using population pharmacokinetics modeling software P-Pharm.
The mean value for oral plasma clearance (CL/F) was 126.59 ml/hr. The corresponding values for apparent volume of distribution (V/F), t1/2 beta, maximum blood concentration (C max), and time to reach the maximum blood concentration (T max) were 334.12 Lit, 1.98 hr, 40.25 ng/ml, and 1.68 hr, respectively. The observed mean values of V/F of propranolol in the present study were comparable with those reported in the literature. However, the mean values of CL/F of propranolol in current study was significantly higher than those reported in other population (P-value This study has confirmed that the pharmacokinetic differences are not able to justify over-responsiveness of Iranian population to propranolol. Pharmacodynamic differences in responding to beta blocker drugs by Renin secretion or having a different sensibility to beta receptors might play a role in making our population have a different response to propranolol.

Voriconazole is an antifungal triazole, approved for management of invasive fungal diseases in patients. It is absorbed during two hours and its serum levels will be above 90%, based on the underlying factors, when the drug is administered orally. Voriconazole shows a propotional increase in an area under the plasma concentration-time curve (AUC), with increasing dose. Plasma protein binding of voriconazole is approximately 60%. Standard doses of the drug and optimal concentration are not predictable due to voriconazole’s nonlinear pharmacokinetics, drug-drug interactions, age, and genetic polymorphisms of the cytochrome CYP2C19. Therefore, in order to prevent adverse effects and optimize outcomes, therapeutic drug monitoring is highly suggested. The application of linking pharmacokinetic and pharmacodynamics characteristics provides information about the relationships between antimicrobial in vitro susceptibility, dosage, drug concentrations and antimicrobial or toxicological effects. The current review paper presents a comprehensive overview of the relation between pharmacokinetic and pharmacodynamics parameters for voriconazole treatment efficacy.

Clopidogrel is a prodrug that converts in the liver to an active thiol metabolite, which irreversibly inhibits the platelet P2Y12 adenosine diphosphate receptor. It seems that methadone as CYP2C19 inhibitor affects ticlopidine activity in vivo. This study aimed to test the ability of methadone in changing ticlopidine pharmacokinetics.
We conducted a case–control study in 10 subjects. The cases (5 subjects) in our study were addicts who were receiving methadone maintenance treatment (MMT) for preventing opium withdrawal symptoms. The control group were opiate users before starting MMT. In both groups, the patients received clopidogrel (75mg/day) for 5 days. On the 6th day, the subjects returned to the clinic, blood samples were taken up to 12 hours following clopidogrel dosing in case and control groups. Plasma concentration of clopidogrel was measured by GC-MAS. Noncompartmental pharmacokinetic analysis was performed using Microsoft Excel software to estimate PK parameters.
In this study, methadone decreased clopidogrel clearance by 25% and increased the AUC0-inf nearly 1.3 fold during the coadministration of clopidogrel as an antiplatelet drug.
A significant decrease in the clearance of clopidogrel during the coadministration of methadone consistent with a decrease in clopidogrel conversion to its active metabolite and this may decrease its efficacy and may have life-threatening consequences for the patients undergoing clopidogerel maintenance therapy

Genetic polymorphisms of cytochrome p450 in humans are the main cause of differences in the metabolism. The allele and genotype frequencies of CYP2C19 and CYP2C9 have been studied in some Iranian populations. The aim of present study was to examine the frequencies of CYP2C18m1, and CYP2C18m2, alleles in the Mazandarani ethnic group among Iranian Population. In this study, genomic DNA was extracted from leucocytes of one hundred unrelated healthy volunteers. The prevalence of the common variants CYP2C18 m1 and m2 alleles were studied by using high fidelity polymerase chain reaction (HF-PCR) - DHPLC methods. The frequency of CYP2C18 m1 and m2 alleles were 0.0% and 3.0%, respectively. CYP2C18 genotypes wt/wt, wt/m1, wt/m2, m1/m1, m1/m2, and m2/m2 frequencies were 97 %, 0.0 %, 3.0%, 0.0 %, 0.0%, and 0.0%, respectively CONCLUTION: The result of the current study shows that impaired CYP2C18 activity in 03% of our sample population may decrease extra hepatic metabolism of some important drugs such as Phenytoin. It may also affect transdemal delivery of drug substrate for this isoenzyme.

Omeprazole is metabolized predominantly by CYP2C19, a polymorphically expressed enzymes that show marked interindividual and interethnic variation. These variations cause a substantial differences that have been reported in the pharmacokinetics of omeprazole. The aim of the present study was to evaluate the pharmacokinetic parameters of omeprazole in a random Iranian population. From the 20 subjects, only 17 healthy unrelated individuals of either sex (9 females age range 22-24 years) participated in the study. After an overnight fasting, a sample of blood was collected. The subjects received a single oral dose of 40 mg capsule of omeprazole (losec) and blood samples were taken up to 8 hours. Omeprazole was analyzed by the HPLC method and population pharmacokinetic analysis was performed using population pharmacokinetic modelling software P-Pharm. The mean value for apparent plasma clearance (CL/F) was 20.8±6.9 (L.h-1). The corresponding value for apparent volume of distribution (V/F), and t1/2 beta were 21.6±7.5 (L) and 0.8±0.3 (h), respectively. A comparison of the weight normalized V/F and CL/F of omeprazole between males and females revealed that both parameters were significantly higher in females than males (p?0.03). These results show a substantial interindividual variability in omeprazole pharmacokinetics and this might affect the therapeutic effects of omeprazole as reported previously.

Background and Pulmonary arterial hypertension (PAH) is a fatal disease affecting patients in all ages that could result in acute and chronic heart failure with high mortality rate. Oral sildenafil is approved to treat PAH in adults and recently in children. There are limited studies on the pharmacokinetics parameters of sildenafil، therefore، this study was designed to determine the pharmacokinetics properties of sildenafil syrup in pediatric pulmonary hypertension. In this interventional open-label prospective study، 20 children aged between two months to 12 years with PAH were included. The patients received sildenafil syrup 0. 5 mg/kg every 12 hour، which was increased to 2 mg/kg every 12 hour (if necessary) to control the pulmonary hypertension. Minimum treatment period was 12 weeks. A week after initiating therapy or dose change five plasma samples were obtained to determine the pharmacokinetic parameters of sildenafil. The samples were determined by HPLC and the data was analyzed using P-Pharm software. Among the subjects، 17 including nine boys and eight girls completed the study. The mean of sildenafil dose was 1. 6 mg/kg/day and the opened one-compartment was considered as the best pharmacokinetic model. The sildenafil pharmacokinetic parameters were Cl=4. 19±1. 35L/h، t1/2=4. 94±1. 49h and Vd=27. 86±7. 39L. The most prevalent side effect of the drug was hot flash. Pharmacokinetic parameters of sildenafil in children with pulmonary hypertension were similar to adults. The patients easily tolerated sildenafil syrup and no severe or serious side effect was observed. Therefore، sildenafil could be considered as a safe and cheap drug to manage pediatric pulmonary hypertension.

Background and Coronary artery disease (CAD) is the first cause of death in modern societies. It is also the first cause for individual health care cost. Multiple risk factors are mentioned for its development among which elevated uric acid is recently introduced as an inflammatory factor. This study was performed for evaluating the serum uric acid level and severity of CAD determined by coronary angiography in patients with chronic stable angina after considering and adjusting other risk factors such as age, smoking (C.S), hypertension (HTN), hyperlipidemia (HLP) and diabetes mellitus (DM). This cross-sectional analytic study was performed in 200 patients with chronic stable angina to determine the relationship between the level of serum uric acid and severity of coronary atherosclerosis in angiography. Other common cardiovascular risk factors including age, DM, HTN, HLP and C.S were also considered. A total of 78 women (39%) and 123 men (61%) were included in the study. There were no significant differences between sex and risk factors including DM, HTN, HLP, C.S, age and serum uric acid level. In the studied population, the mean severity of coronary atherosclerosis score measured by Gensini score was 15.8± 10.7 and the mean level of uric acid was 10.5±6mg/dl. Significant correlation was seen in severity of coronary atherosclerosis and level of serum uric acid in the study population (r=0.51, 0.537, respectively P<0.0001). Also, there was significant correlation between coronary atherosclerosis severity and HTN, age, DM and HLP. Multivariate analysis showed 15% contribution of serum uric acid level in developing coronary atherosclerosis. This study showed an independent relationship between serum uric acid level and severity of coronary atherosclerosis.

To investigate the pharmacokinetics (PK) and PK- pharmacodynamic (PD) relationship of methadone in a cohort of outpatients undergoing methadone maintenance treatment (MMT).

Sixty male patients undergoing MMT with a mean ±SD methadone daily dosage of 58 ± 34 mg were enrolled in this study. Â 5-ml blood sample was collected before the daily intake of methadone. Âs a PD measure, the Subjective Ôpioid Withdrawal Scale (SÔWS) form was completed immediately after obtaining the blood sample. Blood samples were taken and the forms were completed 4-5 times more (up to 24 hr) after the daily intake of methadone. Plasma methadone was analyzed using HPLÇ. Population PK/PD analysis was performed using population pharmacokinetics modeling software P-Pharm.

Significant decreases (p< 0.05) were observed in the SÔWS scores during 10 hours after methadone intake. The SÔWS had returned to baseline by 24 hr after using methaodone (p= 0.98). Â considerable interindividual variability in the ÇL/F (16 fold), ËÇ50 (3 fold) and Ëmax (6 fold) for methadone was observed.Çonclusion: Withdrawal symptoms were significantly improved in MMT patients after taking methadone and the PD measure was substantially affected by fluctuations in plasma methadone concentration. However, The SÔWS had returned to baseline by 24 hr after using mathadone. Thus, a once daily dosing of methadone may not be suitable for those MMT patients who experience a significant withdrawal disturbance in the latter part of the interdose interval. This may increase the perceived severity of withdrawal and induce a craving for additional opioids.

CYP2D6 is polymorphically expressed enzyme that show marked interindividual and interethnic variation. Phenotyping of CYP2D6 provides valuable information about real-time activity of this important drug-metabolizing enzymes through the use of specific probe drugs. The aim of this study was to identify the CYP2D6 oxidation phenotype with dextromethorphan (DEX) as a probe drug in Mazandarani ethnic group among Iranian population. The study included 71 unrelated healthy volunteers. Dextromethorphan hydrobromide (30 mg) was given orally to healthy subjects and peripheral venous blood samples (10 ml) were taken at 3 hr post-dose. Dextromethorphan and the metabolite dextrorphan (DOR) were analyzed by the HPLC method. The log DEX/DOR metabolic ratio (MR) at 3 hr plasma sample was used as the index of CYP2D6 activity and a value of 0.3 was used as the antimode separating extensive metabolizers (EM) and poor metabolizers (PM) phenotypes. A 560-fold interindividual variation in dextromethorphan MRs was observed in this study. Considering the antimode 0.3 in log scale, 7.04% (5/71) volunteers were identified as PMs. The result showed that the frequency of CYP2D6 PM phenotypes accounted for 7.04% of subjects in our samples. Despite these findings, we propose a further study in larger samples to provide a wider image and to get more valuable information upon pharmacogenetic basis for individual therapy and personalized medicine.