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Bioequivalence and Pharmacokinetics Comparison of Two Formulations of Extended-Release Pentoxifylline Tablets in Healthy Subjects after Fasting and Fed Conditions

The pharmacokinetics and bioequivalence of a newly developed extended-released (ER) tablet containing 400 mg pentoxifylline as a test product was compared with the reference brand product Trental® 400 mg ER tablet produced by Sanofi-Aventis. Two separate studies were conducted simultaneously. The first study was conducted under fasting condition, whereas, the second study was conducted under fed condition; using the same batches of the test and reference products in both studies. In each study, both products were administered to 32 healthy male adult volunteers applying a single-dose, two-treatment, two-period, two-sequence, randomized crossover design with one-week washout period between dosing. Twenty two blood samples were withdrawn from each volunteer over 24 hours period.  Pentoxifylline concentrations were determined in plasma by a validated HPLC method according to FDA Bioanalytical Method Validation Guidance using UV detection and chloramphenicol as internal standard. The lower limit of quantitation of the drug in plasma was 5 ng/ml and the upper limit of quantitation was 500 ng/ml. From the plasma concentration-time data of each individual, the pharmacokinetic parameters; Cmax,  AUC0-t, AUC0-Â¥, Cmax/AUC0-Â¥, Tmax, lZ & T0.5; were calculated applying non-compartmental analysis. Data of the test and reference products were statistically analyzed to test for bioequivalence of the two products, using criteria of FDA and EMEA Guidance.  The pharmacokinetic parameters mentioned above were statistically analyzed by descriptive statistics, ANOVA test and 90% Confidence Interval (CI). ANOVA test involved the calculation of the effects of: treatment, period, sequence and subjects nested in sequence. According to the above guidance, the primary pharmacokinetic parameters used for bioequivalence testing, namely Cmax, AUC0-t and AUC0-Â¥ were also statistically analyzed by ANOVA & CI tests using the corresponding Ln-transformed values. The mean values  Cmax,  AUC0-t , AUC0-Â¥ , Cmax/AUC0-Â¥ , Tmax, lZ & T0.5 for the test formula obtained from the fasting study  were; 144.4 ng/ml,  845.4 ng.hr/ml, 868.4 ng.hr/ml, 0.186 hr-1, 3.29 hr, 0.561 hr-1 and 1.65 hr, respectively; and the mean values of these parameters for the reference formula were; 150.0 ng/ml,  871.1 ng.hr/ml, 893.7 ng.hr/ml, 0.177 hr-1, 3.70 hr, 0.558 hr-1 and 1.59 hr,  respectively.  The mean values of the above mentioned parameters for the test formula obtained from the fed study were; 157.8 ng/ml, 826.5 ng.hr/ml, 853.8 ng.hr/ml, 0.198 hr-1, 5.4 hr, 0.458 hr-1 and 2.06 hr, respectively; and the mean values of these parameters for the reference formula were; 162.1 ng/ml, 869.7 ng.hr/ml, 894.8 ng.hr/ml, 0.196 hr-1, 4.1 hr, 0.525 hr-1 and 1.80 hr, respectively.  Based on criteria of FDA and   EMEA Guidance on Bioavailability and Bioequivalence, the results of the fasting and fed studies demonstrated bioequivalence of the two products under either condition. Accordingly, it is concluded that the newly developed ER tablet containing 400 mg pentoxifylline is bioequivalent to Trental® 400 mg ER tablet produced by Sanofi-Aventis.

Keywords: Pentoxifylline, Pharmacokinetics, Bioequivalence.

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Publication Date
Mon Oct 14 2024
Journal Name
Irish Journal Of Medical Science (1971 -)
Comparison between early and late weight bearing after anterior cruciate ligament reconstruction surgery

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Publication Date
Mon Mar 27 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Lipid Profile and Fasting Blood Sugar Analysis in Patients with Cholelithiasis

Cholelithiasis is one of the commonest surgical problems and one of the most common gastrointestinal diseases throughout the world but its pathogenesis remains unclear. Many theories have been proposed forward to explain the mechanism of stone formation. It is not fully clear if symptomatic gallstone disease is associated with a specific pattern of some biochemical abnormalities, as lipid profile and fasting blood sugar in serum of patients.

This study was designed to estimate lipid profile and fasting blood sugar in the sera of patients with cholelithiasis in comparison with normal individuals (control).

In this study, 104(male=16, female=88) were symptomatic gallstone patients (aged 42.79± 12.18 years), and 38(male=6

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Publication Date
Sun Jul 12 2020
Journal Name
Baghdad Science Journal
Geomagnetic Kp Index and Planetary Magnetosphere Size Relationship: for Mercury and Jupiter During two Types of Geomagnetic Conditions

     Kp index correlates with the many magnetosphere properties, which are used to measure the level of magnetic activity. In the solar system, the two different planets, Mercury with weak magnetic field and Jupiter with strong magnetic field, are selected for this study to calculate the planet's magnetosphere radius (RMP) which represents the size of magnetosphere compared with solar activity through Kp index,  through two types of geomagnetic conditions; quiet and strong for the period (2016-2018). From the results, we found that there are reversible relations between them during strong geomagnetic storms, while there are direct relations during quiet geomagnetic conditions. Also it is found that the

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Publication Date
Fri Nov 11 2022
Journal Name
Al-nisour Journal For Medical Sciences
Spectrophotometric determination of sulfamethoxazole in pure and pharmaceutical formulations

New, easy, simple, and fast spectral method for estimation of sulfamethoxazole (SMZ) in pure and pharmaceutical forms. The proposed method is based on the azotization of the drug compound by sodium nitrite in an acidic medium and then coupling with 2,3dimethyl phenol reagent (DMP) in a basic medium to yield an orange-coloured dye which shows λmax at 402 nm. Different affection of the optimization reaction has been completed, following the classical univariate sequence. The concentration of sulfamethoxazole about (1-15) μg. mL-1 with molar absorptivity of (14943.461) L.mol1 .cm-1 that obeyed Beer’s law. The detection and quantification limits were (0.852, 2.583) μg. mL-1 respectively, while the value of Sandell’s sensitivity (

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Publication Date
Sun Apr 13 2025
Journal Name
Journal Of Baghdad College Of Dentistry
Sonographic evaluation of masseter muscle thickness in bruxist and non-bruxist subjects

Background: Masseter muscle is a jaw closing muscle of the mandible involved in Para functional habits; which include lip and cheek chewing, fingernail biting, and teeth clenching or bruxism which can be classified as awake or sleep bruxism. Patients with sleep bruxism are three to four times more likely to experience jaw pain and limitation of movement than people who do not experience sleep bruxism. The aim of this study is to measure the thickness of the masseter muscle in bruxist subjects and compare it with non-bruxist subjects by using sonography. Materials and Method: Forty Iraqi subjects with age ranged (20-40) divided into two groups according to the presence of bruxism. Clinical examination was made and masseter muscle thickness

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Publication Date
Sun Apr 28 2024
Journal Name
Iraqi Journal Of Agricultural Sciences
COMPARISON OF TWO TYPES OF SENSORS AND THEIR EFFECT ON SPRAY QUALITY PEAR TREES

This study was aimed to reduce the amount of the sprayed solution lost during trees spraying.  At the same time, the concentration of the sprayed solution on the target (tree or bush) must be ensured and to find the best combination of treatments. Two factors controls the spraying process: (i) spraying speed (1.2 km/h, 2.4 km/h, 3.6 km/h), and (ii) the type of sensor. The test results showed a significant loss reduction percentage. It reached (6.05%, 5.39% and 2.05%) at the speed (1.2 km/h, 2.4 km/h, 3.6 km/h), respectively. It was noticed that when the speed becomes higher the loss becomes less accordingly. The interaction between the 3.6 km/h speed and the type of Ultrasonic sensor led to a decrease in the percentage of the spray

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Publication Date
Sat Jun 25 2022
Journal Name
International Journal Of Drug Delivery Technology
Ultrasonic and Electrophysiological Evaluation of Carpal Tunnel Syndrome in Diabetic and Non-diabetic Subjects

Background: Carpal tunnel syndrome (CTS) is the most prevalent upper-limb entrapped neuropathy. A nerve conduction study (NCS) is the simplest method for identifying CTS when combined with a satisfactory clinical assessment and physical assessment. Ultrasound is a beneficial non-traumatic screening approach for CTS and there is a relationship between the NCS tests and the measures of CSA by ultrasound. Objective: to assess whether or not sonographic observations of the median nerve seems to be varied amongst DM and non-DM CTS individual. Patients and methods: The total of 50 non-DM Individuals with CTS and 50 DM individuals with CTS have been included in this study. All individuals were submitted to full medical assessment NCS testi

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Publication Date
Wed Mar 29 2017
Journal Name
Iraqi Journal Of Pharmaceutical Sciences ( P-issn 1683 - 3597 E-issn 2521 - 3512)
Concentration-Dependant Antioxidant Activity of Pentoxifylline in Nitrite-induced Hemoglobin Oxidation Model

         Free radical formation in heme proteins is recognized as a factor in mediating the toxicity of many chemicals. The present study was designed to evaluate the dose-response relationship of the free radical scavenging properties of pentoxifylline in nitrite-induced Hb oxidation. Different concentrations of pentoxifylline were added at different time intervals of Hb oxidation in erythrocytes lysate, and formation of methemoglobin (MetHb) was monitored spectrophotometrically. The results showed that in this model, pentoxifylline successfully attenuates Hb oxidation after challenge with sodium nitrite; this protective effect was found to be not related to the catalytic stage of Hb oxidation, th

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Publication Date
Mon Oct 01 2012
Journal Name
Computers & Mathematics With Applications
Boundary element formulations for the numerical solution of two-dimensional diffusion problems with variable coefficients

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Publication Date
Thu Mar 01 2012
Journal Name
Journal Of Al-nahrain University
Histopathological Studies of the Liver and Kidney in Mice Fed on Smut Wheat Infected with Tilletia

The current study was designed to investigate the effect of Tilletia smut spores on histopathological changes in liver and kidney in mice. Twenty animals were divided into two equal groups, 10 mice each, control group fed on normal diet and the treated groups were fed on a mixture of 50% normal diet with 50% wheat infected with Tilletia for 30 days. Histopathological sections taken from liver and kidney treated with Tilletia revealed several alterations. The changes in liver included, multiple granulomatous lesions, area of coagulation necrosis, vacuolar degeneration in the cytoplasm of hepatocytes, proliferation of hepatocytes with formation of pseudolobull which initiates for procancer. Whereas in the kidney, the changes included

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