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Salem I.I.,International Pharmaceutical Research Center | Najib N.M.,International Pharmaceutical Research Center
Clinical Therapeutics | Year: 2012

Background: Betamethasone is used for its antiinflammatory and immunosuppressive effects in disorders of many organ systems. However, the pharmacokinetic properties of betamethasone in plasma after intramuscular injection of betamethasone sodium phosphate and betamethasone acetate dual-acting suspension need further investigation. Objectives: The main aim of this study was to determine the pharmacokinetic parameters of betamethasone, betamethasone acetate, and betamethasone phosphate after the administration of a single intramuscular dose of the dual-acting suspension to healthy human volunteers. Methods: Two different studies were conducted in healthy males. Volunteers were judged healthy based on their medical history, physical examination, and laboratory test results. Before confinement, all volunteers were tested for freedom from alcohol and drugs of abuse. Following a 10-hour overnight fasting, a single dose of 1 mL of the dual-acting suspension containing 3 mg of betamethasone phosphate and 3 mg of betamethasone acetate was administered by intramuscular injection. Blood sampling covered 48 hours. The plasma samples obtained in the second study were stabilized to enable pharmacokinetic profiling of betamethasone esters. Results: Twenty-four healthy males with mean (SD) age of 27 (6.62) years participated in each study. No incidences of serious adverse events were recorded during the studies. Six mild adverse events were reported in 2 subjects in the second study. One subject suffered from pain at the injection site and insomnia, and another subject complained of heartburn and drowsiness. Betamethasone phosphate appeared to be readily absorbed with a mean AUC 0-t of 96.01 ng/h/mL and an AUC 0-∞ of 97.96 (23.38) ng/h/mL. Betamethasone peak plasma concentration reached a mean t 1/2 of 12.92 hours. Betamethasone acetate was not detected in the volunteers' plasma in either study (total of 2208 plasma samples). Conclusion: The observed pharmacokinetic parameters suggested that the acetate ester, and not the phosphate ester, of betamethasone acts as a prodrug or reservoir for betamethasone, conferring on it sustained- and extended-release characteristics. © 2012 Elsevier HS Journals, Inc. Source

Awidi A.,University of Jordan | Salem I.I.,International Pharmaceutical Research Center | Najib N.,International Pharmaceutical Research Center | Mefleh R.,University of Jordan | Tarawneh B.,University of Jordan
Leukemia Research | Year: 2010

The aims of this study were to validate and compare HPLC and LCMSMS analytical methods and their applicability for the quantitation of imatinib in human plasma.A total of 50 patients with chronic myeloid leukemia (CML) in chronic phase (CP) receiving 400mg/day imatinib were enrolled in the study. Drug levels were determined by HPLC-UV and LCMSMS. HPLC intra-day accuracy ranged from 100.51 to 103.19%. LCMSMS accuracy ranged from 89.72 to 106.29%. The correlation coefficient between both methods was r2=0.96. HPLC can be used for imatinib levels' determinations in patients accurately and precisely. © 2009 Elsevier Ltd. Source

Salem I.I.,International Pharmaceutical Research Center | Najib N.M.,International Pharmaceutical Research Center | Idkaidek N.M.,University of Petra
Clinical Therapeutics | Year: 2010

Background: Loratadine is a long-acting tricyclic antihistamine with selective peripheral histamine H1-receptor antagonist activity. Loratadine 10-mg tablets have been reported to be rapidly absorbed after once-daily administration for 10 days in healthy adult subjects, with a Tmax of 1.3 hours for loratadine and 2.5 hours for its major active metabolite, descarboethoxyloratadine. The t1/2 in normal adult subjects has been reported to be 8.4 hours (range, 3-20 hours) for loratadine and 28 hours for its metabolite. Objective: The aim of this study was to determine the population pharmacokinetics of loratadine after oral administration. Methods: A retrospective analysis was conducted of prior noncompartmental analysis results from healthy white Jordanian male subjects who participated in 2 pharmacokinetic studies. After a 10-hour overnight fast, a single 10-mg loratadine tablet was administered orally followed by 240 mL of water. Blood samples were collected before dosing and at 0.33, 0.66, 1, 1.5, 2, 3, 4, 6, 8, 10, 12, 16, 24, 36, 48, 72, and 96 hours after dosing. Mean and population plasma level profiles were examined. The calculated primary and secondary pharmacokinetic parameters were Vd/F, ke, absorption rate constant, lag time, distribution rate constant, redistribution rate constant, Tmax, and Cmax. Results: A total of 72 healthy male subjects with a mean (SD) age of 23 (3.57) years participated in the 2 studies. The analytical method was linear over the concentration range from 0.10 to 20.00 ng/mL (r > 0.999). The lower limit of quantitation was 0.1 ng/mL with 95% accuracy. Precision, expressed as %CV, was 7.44%. Intraday accuracy ranged from 91.9% to 97.2% at high and low quality control levels, respectively. Interday accuracy ranged from 93.57% (%CV, 4.35%) to 98.78% (%CV, 5.78%), respectively. Population ke, t1/2, absorption rate constant, and absorption t1/2 were 0.19 hour-1, 3.65 hours, 1.31 hours-1, and 0.53 hour, respectively. Distribution rate constant, redistribution rate constant, and lag time were 0.31 hour-1, 0.02 hour-1, and 0.32 hour, respectively. The noncompartmental estimate for Cmax was 3.02 ng/mL, which occurred at 1.30 hours, with a t1/2 of 5 hours and a ke of 0.14 hour-1. No adverse events were recorded during the study. Conclusion: The population t1/2 for loratadine was 3.65 hours in this group of healthy white Jordanian male volunteers, shorter than that observed in previous research. © 2010. Source

Salem I.I.,International Pharmaceutical Research Center | Alkhatib M.,International Pharmaceutical Research Center | Najib N.,International Pharmaceutical Research Center
Journal of Pharmaceutical and Biomedical Analysis | Year: 2011

Two specific liquid chromatography-mass spectrometric (LC-MS/MS) assays were developed and validated for the determination of betamethasone (BET), and its acetate (BA) and phosphate (BP) esters. The plasma and the blood used for the development and validation of these two methods were previously stabilized. Liquid-liquid extraction techniques were used after the addition of prednisolone as internal standard (IS). Samples were chromatographed using C8 column, while mass detection was carried out by electrospray ionization in the positive mode (ESI+). The method was proved linear over a working range 0.50-50.00ng/ml for BET (r 2>0.99), while BA linear range was 1.0-20.0ng/ml (r 2>0.99). Sensitivity was determined as 0.50ng/ml for BET and 1.00ng/ml for BA. Betamethasone phosphate LC-MS/MS method involved solid phase extraction after the addition of prednisolone phosphate as (IS). Separation was carried out using C18 column, while detection was by ESI+. The method showed good linearity over the working range 2.0-200.0ng/ml (r 2>099). Both methods were applied to determine BET, BA and BP in plasma samples obtained for pharmacokinetics studies in human. © 2011 Elsevier B.V. Source

Zaater M.F.,Jordan University of Science and Technology | Tahboub Y.R.,Jordan University of Science and Technology | Ghanem E.,International Pharmaceutical Research Center
Journal of Chromatographic Science | Year: 2012

A selective, sensitive and stability-indicating reversed-phase high-performance liquid chromatography method was developed and validated for the determination of clarithromycin antibiotic in human plasma. Liquid chromatography was performed on a 5-m (100 × 4.6 mm) C8 column at 40°C. The mobile phase consisted of acetonitrile with 0.045M H 3PO4 (37:63, v/v) adjusted to pH 6.7 and pumped at a flow rate of 1.2 mL/min. Detections were monitored on an electrochemical detector operated at a potential of 0.85 V with glassy carbon electrode against Ag/AgCl reference electrode. Each analysis required 13 min and quantification over the range of 0.05-5.0 g/mL of plasma was linear, as indicated by a correlation coefficient (R2), 0.9999.The method was validated according to international guidelines. Data with respect to accuracy, within-run and between run, were close to 100 with 4 precision. Absolute recovery was 95. The limit of quantification was 0.05 μg/mL. Neither endogenous substances nor commonly used drugs were found to interfere with the retention times of analytes. Stock solutions and calibration standards of the drug and quality control preparations were demonstrated to be stable at room temperature and -20°C for long and short periods of time. Eventually, the proposed method was successfully applied to quantify clarithromycin in spiked human plasma and real samples from healthy volunteers, indicating the utility and throughput of this method for clinical and bioavailability studies. © 2012 The Author. Published by Oxford University Press. All rights reserved. Source

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