Jordan Center for Pharmaceutical Research

Amman, Jordan

Jordan Center for Pharmaceutical Research

Amman, Jordan

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Arafat T.,Jordan Center for Pharmaceutical Research | Payne D.,University of Manchester | Ollier W.,University of Manchester | Pushpakom S.,University of Manchester | And 2 more authors.
European Journal of Clinical Pharmacology | Year: 2010

This study provides the first analysis of the TPMT mutant allele frequency in a sample of the Jordanian population and indicates that TPMT*3A is the most common allele in Jordanian subjects. Purpose: Thiopurine methyltransferase TPMT catalyses the S-methylation of thiopurine drugs such as 6-mercaptopurine, 6-thioguanine, and azathiopurine. Thiopurine methyltransferase (TPMT) polymorphisms are the major determinants of interindividual differences in the severe haematological toxicity of 6-mercaptopurine. Several variants in the TPMT gene have been identified that correlate with a low activity phenotype. Four variant alleles, TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C, are responsible for over 80% of the low or undetectable enzyme activity. The allelic frequency of TPMT variants has been established in many populations. Methods: In this study, the frequencies of four (TPMT*2, TPMT*3A, TPMT*3B and TPMT*3C) variants were investigated in 169 healthy Jordanian men (18-45 years of age). Single nucleotide polymorphisms (SNPs) were genotyped using the Sequenom® MassARRAY technology (Sequenom®; San Diego, CA, USA). Results: TPMT*3A and TPMT*3C were the only deficiency alleles detected in the Jordanian population with an allele frequency of 0.59% and 0.30% respectively. The TPMT*3A allele frequency is found to be lower than in the European Caucasian population. Conclusion: TPMT*3A and TPMT*3C were the only deficiency alleles detected in the Jordanian population with an allele frequency of 0.59% and 0.30% respectively. The TPMT*3A allele frequency is found to be lower than in the European Caucasian population. © 2010 Springer-Verlag.


Eftaiha A.F.,Suwagh Company for Drug Delivery Systems | Qinna N.,Suwagh Company for Drug Delivery Systems | Qinna N.,University of Petra | Rashid I.S.,Suwagh Company for Drug Delivery Systems | And 4 more authors.
Marine Drugs | Year: 2010

Metronidazole, a common antibacterial drug, was incorporated into a hydrophilic polymer matrix composed of chitosan xanthan gum mixture. Hydrogel formation of this binary chitosan-xanthan gum combination was tested for its ability to control the release of metronidazole as a drug model. This preparation (MZ-CR) was characterized by in vitro, ex vivo bioadhesion and in vivo bioavailability study. For comparison purposes a commercial extended release formulation of metronidazole (CMZ) was used as a reference. The in vitro drug-release profiles of metronidazole preparation and CMZ were similar in 0.1 M HCl and phosphate buffer pH 6.8. Moreover, metronidazole preparation and CMZ showed a similar detachment force to sheep stomach mucosa, while the bioadhesion of the metronidazole preparation was higher three times than CMZ to sheep duodenum. The results of in vivo study indicated that the absorption of metronidazole from the preparation was faster than that of CMZ. Also, MZ-CR leads to higher metronidazole Cmax and AUC relative to that of the CMZ. This increase in bioavailability might be explained by the bioadhesion of the preparation at the upper part of the small intestine that could result in an increase in the overall intestinal transit time. As a conclusion, formulating chitosan-xanthan gum mixture as a hydrophilic polymer matrix resulted in a superior pharmacokinetic parameters translated by better rate and extent of absorption of metronidazole. © 2010 by the authors; licensee MDPI.


Zalloum I.,University of Jordan | Hakooz N.,University of Jordan | Hakooz N.,Zarqa University | Arafat T.,Jordan Center for Pharmaceutical Research | Arafat T.,University of Petra
Molecular Biology Reports | Year: 2012

To relate the pharmacokinetics of orally administered lansoprazole in healthy adult Jordanian men with CYP2C19 polymorphisms and to determine the percentage of CYP2C19 polymorphism in Jordanian population and the allelic frequency of CYP2C19*2 and CYP2C19*3. A total of 78 healthy Jordanian volunteers were included in this study from three different bioequivalence studies, one of these studies which included 26 volunteers was done on lansoprazole. Genotyping for CYP2C19*1, CYP2C19*2, CYP2C19*3 was done for all 78 volunteers, the data of genotyping of all subjects used for screening the frequency of different genotypes and the allelic frequency of different polymorphisms in healthy Jordanian men, the pharmacokinetics and genotyping data for the study of lansoprazole was matched and compared to investigate presence of statistical differences in pharmacokinetic parameters. In Jordanian subjects, the allele frequencies of the CYP2C19*2 and CYP2C19*3 mutation were 0.16 and 0, respectively. The concentration-Time curves in the two groups [homozygote extensive metabolizer (homEM, n = 19) and heterozygote extensive metabolizer (homEM, n = 7)] groups were fitted to a non-compartment model. In the homEM and in the hetEM groups, the main kinetic parameters were as follows: Tmax (2.1875 ± 0.777) and (2.54 ± 1.87) h, Cmax (697.875 ± 335) and (833.58 ± 436.26) mg/l, t1/2 (1.3 ± 0.43) and (2.38 ± 1.64) h, AUC(0) were (1,684.9 ± 888) and (3,609.8 ± 318) mg h l-1, respectively. The Jordanian population showed similarities in CYP2C19 allele and genotype distribution pattern with Caucasians and Africans. CYP2C19 allele and poor metabolizer (PM) genotype frequencies in the Jordanian population are distinct from populations' from East Asia such as Japanese and Koreans. Although lower pharmacokinetic parameters were found in homEM compared to hetEM but there was no significant difference between the two groups (P<0.05). © Springer Science+Business Media B.V. 2011.


Diab O.,University of Jordan | Arafat T.,Jordan Center for Pharmaceutical Research | Arafat T.,University of Petra | Yousef A.-M.,University of Jordan
Tropical Journal of Pharmaceutical Research | Year: 2015

Purpose: To assess the influence of smoking cigarettes on the pharmacokinetics of the antiplatelet drug, clopidogrel. Methods: Thirty four male patients, mean age and weight of 59.3 years and 81.1 kg, respectively, who underwent percutaneous coronary intervention (PCI), took part in the study. Each subject received an oral loading dose of 600 mg clopidogrel eight tablets, each 75 mg). Clopidogrel carboxylate plasma level was measured and non-compartmental analysis was used to determine peak plasma concentration (Cmax), time to achieve peak plasma concentration (Tmax), elimination half-life (t1/2e), and area under the curve (AUC0-∞). Other parameters measured include gamma-glutamyltransferase enzyme (GGT), low density lipoprotein cholesterol (LDL-cholesterol), blood urea nitrogen (BUN) and platelet count. Results: Nineteen patients were smokers (55.9 %). Smokers had higher levels of GGT compared to non-smokers (31.73 ± 14.42 vs. 21.63 ± 11.41 IU/L, p = 0.08) as well as higher levels of LDL-cholesterol (116.79 ± 42.08 vs. 87.07 ± 27.34 mg/dl, p = 0.041, respectively). Smokers had shorter half-life (smokers: 3.47 ± 1.9 h vs. non-smokers: 5.83 ± 4.09 h, p = 0.012). Smoking behavior had no influence on Cmax (p = 0.16), AUC0-∞ (p = 0.65) or Tmax (p = 0.91). In general, the pharmacokinetic parameters were characterized by considerable inter-individual variation (Cmax = 23.2 ± 8.79 μg/ml, coefficient of variation (CV) = 37.9 %), (Tmax = 1.71 ± 1.15 h, CV = 67.2 %), (AUC0-∞ = 120.97 ± 44.4 μg.h/ml, CV = 36.7 %) and (t1/2e = 4.57 ± 3.15 h, CV = 68.9 %). Conclusion: Smoking behavior may not be a significant determinant of the pharmacokinetics of clopidogrel following oral administration of 600 mg dose in patients undergoing PCI. © Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, 300001 Nigeria. All rights reserved.


Aqel S.M.,University of Jordan | Irshaid Y.M.,University of Jordan | Gharaibeh M.N.,University of Jordan | Arafat T.A.,Jordan Center for Pharmaceutical Research
Drug Metabolism Letters | Year: 2011

The effect of ethyl acetate extract of pomelo fruit on systemic exposure of verapamil was explored in rabbits. Two groups each of 8 locally-inbred New Zealand male rabbits were used. The first group was used for single-dose treatment (both verapamil and pomelo extract). The second group was used for multiple-dose treatment, pomelo extract (once daily for 14 days) and verapamil single doses (at days 7 and 14). A verapamil dose of 30 mg/kg and a pomelo extract dose of 45 mg/kg were used. Single-dose treatment with pomelo extract resulted in a minor change in mean Cmax of verapamil in plasma, while a decrease of 37.8% in AUC0-24 and 28.3% in AUC0-∞ was observed but did not reach statistical significance. After the first period of multiple dose treatment (pomelo extract for 7 days), the combination increased the concentration of verapamil in plasma with a significant increase in mean Cmax, AUC0-24 and AUC0-∞ by 461.9%, 299.7%, and 261.1%, respectively (p values were 0.005, 0.002, and 0.006, respectively). In contrast, after the second period (day 14 of pomelo extract use), the combination decreased the concentration of verapamil in the plasma with a substantial decrease in mean Cmax, AUC0-24, and AUC0-∞, by 68.2%, 69.7% and 58.3%, respectively. This decrease did not reach statistical significance (p values were 0.073, 0.081 and 0.083, respectively). The Tmax was not affected significantly in both studies. The study illustrates a complex time-dependent interaction between verapamil and the ethyl acetate extract of pomelo mix. More intensive studies are needed to further understand the nature of the interaction. © 2011 Bentham Science Publishers Ltd.


Yacoub M.,Jordan Center for Pharmaceutical Research | awwad A.A.,Jordan Center for Pharmaceutical Research | Alawi M.,University of Jordan | Arafat T.,University of Petra
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2013

A simple liquid chromatography/ion trap mass spectrometry method for the quantification of amlodipine and atorvastatin with its metabolites, ortho and para hydroxy atorvastatin, simultaneously in human plasma was developed. Analytes with internal standard were extracted by protein direct precipitation with acetonitrile. Adequate chromatographic separation was achieved using Phenomenex Synergi 4u polar-RP 80A (150mm×4.6mm, 4μm) column in the isocratic elution mode and the eluent was water/methanol (14:86%, v/v) adjusted by trichloroacetic acid to pH 3.2 which was delivered isocratically at constant flow rate of 0.50mL/min. Standard solutions for the analytes were prepared using amlodipine besylate, atorvastatin calcium, ortho-hydroxy atorvastatin dihydrate monosodium salt, para-hydroxy atorvastatin disodium salt, and pravastatin sodium as an internal standard. The method validation intends to investigate specificity, sensitivity, linearity, precision, accuracy, recovery, matrix effect and stability according to USFDA guideline. Standard calibration levels were prepared by pooled human plasma to attain final dynamic range of 0.2-20.0ng/mL for amlodipine, 1.5-150ng/mL for atorvastatin, 1.0-100.0ng/mL for ortho-hydroxy atorvastatin and 0.2-20.0ng/mL for para-hydroxy atorvastatin. Clinical bioequivalence study was successfully investigated by the application of this validated bioanalytical method in order to evaluate bioequivalence of two commercial products 10mg amlodipine/80mg atorvastatin in a single dose. In this study, 29 healthy volunteers were participated in randomized, two periods, double blend, open label cross over design. Pharmacokinetic parameters of Cmax, AUC0-t and AUC0-∞ were calculated to compare a test product with CADUET® reference product. © 2013 Elsevier B.V.


Al-Deeb I.D.,University of Jordan | Arafat T.A.,Jordan Center for Pharmaceutical Research | Irshaid Y.M.,University of Jordan
Drug Metabolism Letters | Year: 2010

The effect of licorice root drink (aqueous extract of Glycyrrhiza glabra Fabaceae) on plasma concentration of verapamil, using rabbits as animal model, was investigated. Two groups of locally inbred Newzeland male rabbits were used. The first group was given a single dose of licorice drink (4 ml/kg body weight) concomitantly with 30 mg/kg verapamil, and the second group was given a daily dose of licorice drink (4 ml/kg body weight) for two weeks, with single doses of verapamil on days, 7 and 14. Single dose treatment resulted in a nonsignificant decrease in mean C max by 33.2% (P = 0.41), but in a significant decrease of AUC 0-24 and AUC 0-∞ by 60.5% and 63.6%, respectively (P = 0.01). First period of multiple dose treatment study (7 days), resulted in a significant reduction in mean C max, AUC 0-24 and AUC 0-∞ by 55.0%, 47.0% and 45.7%, respectively (P = 0.02, 0.03 and 0.03, respectively). A more pronounced effect was seen at second period of multiple dose treatment study (14 days), where the corresponding decrease was, 85.4%, 76.8% and 73.3%, respectively (P < 0.01). Mean T max was significantly increased 4.2-fold over control period at day 14 of multiple dose study (P = 0.02). In conclusion, licorice root drink decreased verapamil systemic exposure both after single dose and after daily doses for 14 days. © 2010 Bentham Science Publishers Ltd.


Hakooz N.,University of Jordan | Hakooz N.,Zarqa University | Alzubiedi S.,University of Jordan | Yousef A.-M.,University of Jordan | And 4 more authors.
Molecular Biology Reports | Year: 2012

Glucuronidation is one of the most important phase II metabolic pathways. It is catalyzed by a family of UDP-glucuronosyltransferase enzymes (UGTs). One of the subfamilies is UGT1A. Allele frequencies in UGT1A4 differ among ethnic groups. The aim of this study was to determine the allelic frequency of two most common defective alleles: UGT1A4*2 and UGT1A4*3 in a Jordanian population. A total of 216 healthy Jordanian Volunteers (165 males and 51 females) were included in this study. Genotyping for UGT1A4*1, UGT1A4*2 and UGT1A4*3 was done using a well established polymerase chain reaction-restriction fragment length polymorphism test. Among 216 random individuals studied for UGT1A4*2 mutation there were 26 individuals who were heterozygous, giving a prevalence of 12% and an allele frequency of 6.5%. Only one individual was homozygous for UGT1A4*2. The UGT1A4*3 mutation was detected as heterozygous in 9 of 216 individuals indicating a prevalence of 4.2% and allele frequency of 3.5%. Three individuals were homozygous for the UGT1A4*3 indicating a prevalence of 1.4%. The prevalence of UGT1A4*2 is similar to the Caucasians but different from other populations whilst the UGT1A4*3 prevalence in the Jordanian population is distinct from other populations. Our results provide useful information for the Jordanian population and for future genotyping of Arab populations in general. © 2012 Springer Science+Business Media B.V.


Arafat T.,University of Petra | Arafat B.,Al-Ahliyya Amman University | awad R.,University of Petra | awwad A.A.,Jordan Center for Pharmaceutical Research
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences | Year: 2014

A simple and sensitive liquid chromatography-tandem mass spectrometric method for quantification of loperamide in human plasma and saliva was developed and validated, and then successfully applied in pharmacokinetic clinical study to investigate and correlate bioavailability of Imodium® 2mg quartet tablet dose in both human plasma and saliva. Loperamide with labeled internal standard was extracted from its biological matrix by methanol as protein direct precipitant in single extraction step. Adequate chromatographic separation for analytes from plasma and saliva matrices was achieved using ACE C18 (50mm×2.1mm, 5μm) column, eluted by water/methanol/formic acid (30:70:0.1%, v/v), delivered isocratically at constant flow rate of 0.75ml/min. The method validation intends to investigate specificity, sensitivity, linearity, precision, accuracy, recovery, matrix effect and stability according to European guideline, and partial validation was applied on saliva, specificity, matrix effect, recovery, sensitivity, within and between day precision and accuracy. The calibration curve was linear through the range of 20-3000pg/ml in both plasma and saliva using a 50μl sample volume. The partial validation sections outcome in saliva was so close to those in plasma. The within- and between-day precisions were all below 8.7% for plasma and below 11.4% for saliva. Accuracies ranged from 94 to 105% for both matrices. In this study, 26 healthy volunteers participated in the clinical study, and 6 of gave their saliva samples in addition to plasma at the same time schedule. The pharmacokinetic parameters of Cmax, AUC0-t and AUC0-∞, Tmax and T1/2 in both plasma and saliva were calculated and correlated. © 2014 Elsevier B.V.

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