Population Pharmacokinetics Modeling of Lamotrigine in Jordanian Epileptic Patients Using Dried Blood Spot Sampling.

AIMS: To characterize the population pharmacokinetics of lamotrigine in Jordanian epileptic patients and to identify factors affecting therapeutic parameters. PATIENTS AND METHODS: A population pharmacokinetics model for lamotrigine was established based on a prospectively collected data of 52 steady-state concentrations from 38 adult and pediatric patients with epilepsy. Lamotrigine concentrations were determined by a dried blood spot liquid chromatography method. Data were analyzed according to a one-compartment model with first-order absorption and elimination using the nonlinear mixed effect modeling program. The covariates effect of total body weight, gender, age, and co-medication with topiramate, carbamazepine, phenytoin, phenobarbital, and valproic acid on lamotrigine clearance were investigated using a stepwise forward addition followed by a stepwise backward elimination. RESULTS: The final population pharmacokinetics model for lamotrigine clearance was as follows: CL/Fpop=θ1*exp (θ3*age)*exp (θ5*carbamazepine)*exp (θ6*valproic acid) , where θ1 is the relative clearance (L/hr) estimated, and θ3, θ5, and θ6 are the fixed parameters relating to age and co-medication with carbamazepine and valproic acid, respectively.The population mean value of lamotrigine total clearance generated in the final model (with covariates) was 2.12 L/hr. Inter-individual variability and residual unexplained variability expressed as the coefficient of variation was 37.1 and 26.1%, respectively. CONCLUSION: Lamotrigine total clearance in the Jordanian patients is comparable to that reported by others for Caucasian patients. Age and concomitant therapy with carbamazepine and valproic acid significantly affected lamotrigine clearance, and accounted for 48% of its inter-individual variability.

The effects of pummelo juice on pharmacokinetics of sildenafil in healthy adult male Jordanian volunteers.

PURPOSE: The main purpose of this work was to investigate the effect of pummelo juice on the pharmacokinetics of sildenafil after oral administration. METHODS: This was a comparative, randomized, two-period, two-treatment, two-sequence, single dose, crossover study investigating the effect of pummelo juice on the pharmacokinetics of sildenafil citrate tablets (equivalent to 50 mg sildenafil) in healthy male participants under fasting conditions compared with water as a control. Six healthy normal adult males were administered 50 mg sildenafil with pummelo juice or water at two different periods in a crossover study. RESULTS: Study results showed that pummelo juice reduced the rate and extent of sildenafil bioavailability to around 60% [maximum plasma concentration (C(max)); from 212.44 ng/ml to 134.07 ng/ml, 90% confidence interval (90% CI) 44.70-89.11, and area under the plasma concentration time curve from zero to infinity (AUC(infinity)); from 564.51 ng.hr/ml to 336.87 ng.hr/ml, 90% CI 39.17-90.92]. This interaction was opposite to that expected and is speculated to be due to either an effect on transporters or a physicochemical interaction between sildenafil and some components of the juice. CONCLUSION: Patients should be advised not to drink pummelo juice before or immediately after taking sildenafil.

Antiplatelet therapy for primary and secondary prevention in Jordanian patients with diabetes mellitus.

INTRODUCTION: Guidelines for diabetes treatment recommend the routine use of aspirin in patients with diabetes mellitus (DM) who have cardiovascular disease (CVD), those with at least one CVD risk factor, and for anyone with DM who is>30 years of age or, if contraindicated, an alternative antiplatelet agent. We evaluated the adherence to these recommendations in a subset of diabetic patients in Jordan, and identified physician and patient characteristics associated with the use of antiplatelet therapy. MATERIALS AND METHODS: A cross-sectional observational study conducted in randomly selected outpatient clinics. The study included 199 adult patients with DM who were eligible for antiplatelet prophylaxis. Review of medical charts and direct interviews with patients were performed to obtain information on demographic characteristics of the patients, clinical factors and medication prescription. Bivariate analysis and multivariate logistic regression methods were used to determine what factors were related to antiplatelet drug use. RESULTS: Among diabetic patients eligible for antiplatelet prophylaxis, the prevalence of antiplatelet drug use for primary or secondary prevention was 84%. Factors associated with antiplatelet prophylaxis were male gender (odds ratio, OR 2.97), presence of angina (OR 3.00), history of myocardial infarction (OR 3.75), history of coronary revascularization (OR 3.12), five or more prescription medications (OR 4.61), and physician's specialty other than endocrinology ( OR 4.35). CONCLUSIONS: Adherence rates to the international guidelines regarding routine antiplatelet prophylaxis in adults with DM who are eligible for such prophylaxis are suboptimal. Efforts towards increasing these rates of antiplatelet prophylaxis are necessary.

Assessment of anti-factor Xa activity of enoxaparin for venous thromboembolism prophylaxis in morbidly obese surgical patients.

BACKGROUND: Venous thromboembolism (VTE) can be encountered by 60% of hospitalized patients. Anticoagulants have been recommended to reduce the risk of VTE in patients with risk factors. However, no specific dosing recommendations for obese patients are provided in the current practice guidelines. The purpose of this study was to determine the efficacy and safety of weight-based dosing of enoxaparin for VTE prophylaxis among morbidly obese patients undergoing surgery. METHODS: Adult patients were enrolled if they have a body mass index (BMI) of ≥35 kg/m2 and were scheduled for surgery. These patients were prescribed enoxaparin (0.5 mg/kg subcutaneously [SC] once daily). Peak anti-factor Xa levels were measured 4 h after the third dose of enoxaparin. The primary outcome measure was to determine whether a weight-based dosing of enoxaparin of 0.5 mg/kg produce the anticipated peak anti-Xa levels (0.2-0.6 IU/m) among obese patients undergoing surgery. Secondary outcomes include the incidence of VTE, the incidence of minor or major bleeding, and the incidence of heparin-induced thrombocytopenia (HIT). RESULTS: Fifty patients were enrolled in the study. The mean age was 53 ± 16 years, 74% of the patients were female. The mean BMI was 40.5 ± 5, and the average enoxaparin dose was 50 ± 9.8 SC daily. Nearly 88% of the patients reached the target anti-factor Xa (0.427 ± 0.17). None of the patients developed HIT or VTE. There was no incidence of major or minor bleeding. CONCLUSIONS: Weight-based enoxaparin dose led to the anticipated peak anti-Xa levels (0.2-0.6 IU/mL) in most of the morbidly obese study patients undergoing surgery without any evidence of major side effects. The weight-based dosing of enoxaparin was also effective in preventing VTE in all patients. Although these results are promising, further comparative trials are needed in the setting of morbidly obese surgical patients.

Assessment and comparison of CHADS2, CHA2DS2-VASc, and HAS-BLED scores in patients with atrial fibrillation in Saudi Arabia.

AIMS: No previous reports on the utilization of CHADS2, CHA2DS2-VASc, and HAS-BLED scores in atrial fibrillation (AF) patients in Saudi Arabia have been identified in the literature. The main objectives of this study were to assess and compare the distribution of CHADS2, CHA2DS2-VASc, and HAS-BLED scores and to identify the most common risk factors for stroke and bleeding among AF patients attending clinical pharmacists managed anticoagulation clinic. SETTINGS AND DESIGN: This cross-sectional study was conducted over 2 months period at clinical pharmacists managed anticoagulation clinic. METHODS: CHADS2, CHA2DS2-VASc, and HAS-BLED scores were calculated and compared for all eligible patients. RESULTS: Two hundred and sixty-four patients with AF were included in the analysis. The number of patients at low risk for stroke was found to be 14 (5.3%) using CHADS2 and only 4 (1.5%) using CHA2DS2-VASc. On the other hand, 64 patients (24.2%) were found at moderate risk for stroke using CHADS2 compared with 17 patients (6.4%) using CHA2DS2-VASc. Most of the patients were found to be at high risk for stroke using either the CHADS2 (70.5%) and CHA2DS2-VASc (92%). The study also revealed that most of the patients were at moderate (63.3%) to high (27.7%) risk of bleeding. CONCLUSIONS: The results of this study show that the percentage of patients at high risk for stroke and bleeding is very high. The study revealed that this could be attributed to the high prevalence of modifiable risk factors for stroke and for bleeding in Saudi patients with AF.

Validation of the Arabic version of the revised Fibromyalgia Impact Questionnaire (FIQR_A) on Jordanian females with fibromyalgia.

The aim of this study was to translate and validate the Arabic version of the Revised Fibromyalgia Impact Questionnaire (FIQR_A). Translation of the FIQR followed a worldwide-recognized approach to ensure the accuracy and equivalency of the translation from the English version of the FIQR. Following the translation of the FIQR, 92 women with fibromyalgia completed the FIQR_A, the Arabic Research ANd Development Short Form Health Survey (RAND SF-36), and the Arabic Hospital Anxiety and Depression Scales (HADS). The FIQR_A significantly correlated with RAND SF-36 domains and HADS. The correlations ranged from fair to moderate. For selected outcomes, Bland-Altman plots were consistent with Spearman's correlations. Test-retest intraclass correlation coefficients were all significant and ranged from moderate to excellent. Internal consistency was found to be excellent. These observations suggest that the FIQR_A is a valid and reliable tool for both clinical practice and research purposes with Arabic speakers globally.

Evaluation of the impact of pharmaceutical care service on hospitalized patients with chronic kidney disease in Jordan.

OBJECTIVES: The primary goal of the present study was to implement and evaluate the impact of pharmaceutical care service for hospitalized chronic kidney disease (CKD) patients in Jordan. SETTING: Nephrology wards of one of the largest general hospitals in Jordan. METHODS: All patients who were previously diagnosed with CKD by their physician were eligible for inclusion in the study. Recruited patients were fully assessed for treatment related problems (TRPs) by a clinical pharmacist. Pharmaceutical care service was assessed through a systematic, prospective before-after design. Chi Square test was used to investigate association between categorical variables. P value <0.05 was considered to be statistically significant. MAIN OUTCOME MEASURES: Study outcomes included: Process outcomes (prevalence and nature of identified TRPs, clinical significance of TRPs, associated diseases and drugs), General clinical outcomes (Therapeutic outcomes of TRPs) and CKD specific clinical outcomes (Change from baseline in the number of patients receiving appropriate progression modifying therapy and appropriate management of complications). RESULTS: 130 patients were included in the study. The average number of the identified TRPs was 5.31. Eighty-six percent of the recommendations were accepted by physicians. Efficacy related problems were the most common TRP category. Seventeen percent of all TRPs were resolved, 5.5 % were improved, and 37.4 % were prevented through the clinical pharmacist interventions. CONCLUSIONS: The current study indicated that hospitalized patients with CKD suffer from multiple TRPs mostly related to efficacy of medications and patients monitoring. Clinical pharmacists substantially contributed towards the care of hospitalized CKD patients through optimizing progression modifying therapies, medications safety and management of CKD complications. Based on this study it is strongly recommended to implement pharmaceutical care services for hospitalized CKD patients.

Comprehensive assessment of treatment related problems in hospitalized medicine patients in Jordan.

OBJECTIVES: The aim of this study was to identify the prevalence and characteristics of treatment related problems (TRPs) in hospitalized internal medicine patients in Jordan as well as to identify diseases and drugs associated with each specific TRP. We have also aimed at investigating physicians' acceptance of recommendations made by clinical pharmacist and to identify the outcomes of pharmacist interventions. SETTING: Internal medicine department of a general hospital in Jordan. METHODS: We have utilized a systematic, prospective, bedside, comprehensive clinical assessment approach that allowed us to effectively identify, communicate and follow up TRPs. MAIN OUTCOME MEASURES: prevalence and nature of identified TRPs, clinical significance of TRPs, associated diseases and drugs and clinical outcomes of clinical pharmacist interventions. RESULTS: 402 patients were included in the study. The average number of the identified TRPs was 9.35. Fifty-three percent of identified TRPs were classified as major and 28% were classified as moderate. Ninety-one percent of the recommendations were accepted by physicians. Efficacy related problems were the most common TRP category followed by safety related problems and indication related problems. Sixty-four percent of the TRPs were resolved or prevented through the clinical pharmacist intervention. CONCLUSIONS: We have found that prevalence of TRPs is substantially high among patients hospitalized at the internal medicine department. TRPs related to Dosage regimens, untreated conditions, patient monitoring, drug interactions, and drug choices were the most common. Most of TRPs identified by pharmacists were clinically significant. Pharmacists' interventions contributed substantially to the resolving of many of the identified TRPs. Patients suffering from higher number of medical conditions and receiving higher number of medications should be given the priority for clinical pharmacy service in hospitalized internal medicine patients.

Development and validation of the Arabic allergic rhinitis quality of life questionnaire.

OBJECTIVE: To develop and validate an Arabic allergic rhinitis quality of life questionnaire (AAQQ). METHODS: The study was conducted at the Ear, Nose, and Throat Clinic at the University of Jordan Hospital, Amman, Jordan, from February 2006 to June 2007. A questionnaire was developed from data obtained from 90 patients, and the validation study was conducted on 140 patients. The study was a 5-week observational study. We evaluated the measurement properties necessary for use of the AAQQ in clinical practice, clinical trials, and cross-sectional surveys. RESULTS: The intraclass correlation coefficient for the repeated AAQQ measurements was excellent (0.93), indicating a very high reliability and repeatability of the instrument. Cross-sectional correlations and longitudinal construct validity between the AAQQ and the other measures of health status was close to the priori predictions, and similar to those obtained in the literature for similar scales. The responsiveness index for the AAQQ was high (1.04), and higher than that reported for similar instruments. CONCLUSION: The results from the validation study provide evidence that the AAQQ has strong discriminative and evaluative measurement properties, and can be used in patient monitoring, cross-sectional surveys, and clinical trials. The AAQQ has the combined advantage of being short, and contains the most important items and domains.

Validation of a comprehensive classification tool for treatment-related problems.

OBJECTIVE: Several drug-related problem classification systems can be found in the literature. However, it is generally agreed that a comprehensive, well constructed and validated instrument is currently lacking. The aim of this study is the development and validation of a comprehensive treatment-related problems assessment and classification tool for use in teaching, practicing and researching pharmaceutical care and to improve identification, resolving and preventing of treatment-related problems. METHOD: The development and validation involved five steps starting with literature search to define a treatment related problem and also to form a database of treatment-related problems identified in the literature. In the next step, all problems that were identified in the first step and passed the evaluation of the three authors were pooled together and then divided into groups according to their common or shared construct, in the third step a suitable assessment method was developed according to the construct of the different problems, in the next step the developed instrument was validated for content, internal and external validity. Finally the tool was finalized and tested for reproducibility and inter-rater agreement. RESULTS: The final validated version included six main categories for treatment-related problems (Indication, Effectiveness, Safety, Knowledge, Adherence and Miscellaneous). These categories include a total of nine subcategories and a total of 29 treatment related problems. CONCLUSION: The treatment-related problems assessment and classification tool introduced in this paper was applied to actual patient cases and proved to be valid. This tool also has several features that are new.