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.

Prevalence of Cardiovascular Diseases Risk Factors among Jordanians.

BACKGROUND AND AIMS: One of the most common causes of death worldwide is cardiovascular diseases (CVDs). This study evaluated the prevalence of CVDs risk factors (RFs) and their constellation electively among the Jordanian population and, assessing the most prevalent RF interplay with the rest of CVDs RFs as well as the impact of age and gender dimorphism on the frequencies of coexistence of multiple CVDs risk factors (RFs) among the Jordanian population. METHODS AND RESULTS: In this observational multicenter study, a total of 1449 subjects were enrolled. The mean age (±SD) was 44.35 ± 14.46 years; 796 (54.9%) of them were females and 801 (55.28%) of the whole study pool had no family history of premature CVDs. Only 5.9% of the population did not have any of these RFs. The prevalence of CVDs MRFs within-affected subjects was as follows: there were 1081 (74.6%) subjects with overall dyslipidemia, 471 (32.51%) with obesity, 456 (31.47%) were smokers, and at the first diagnostic encounter 541 (37.47%) were with elevated blood pressure and, 310 (21.51%) were with elevated random blood sugar. The coexistence of ≥ two, ≥ three and, ≥ four RFs was observed in 75.7%, 44.4%, and 21.4% of the subjects, respectively. The constellation of multiple RFs was more frequent in men than that in women, where the presence of ≥ two RFs for men was at 86.18% vs. 67.09% for women. Similarly, the appearance of multiple RFs increases with age, starting from the existence of ≥ three, and four RFs respectively. Most notably the clustering of ≥ five RFs in the age group of 45-59 years showed the greatest frequency vs. any other age group. CONCLUSIONS: CVDs risk factors (RFs) and clusters of them are extremely prevalent in the Jordanian population. Overall dyslipidemia is the most prevalent MRF and the most favors clustering with other CVDs RFs. Combined two RFs had the highest proportional frequency between all six RFs clusters. The constellation of at least two, three, and four CVDs RFs presented at almost three-fourth, half, and around one-fourth; respectively, Middle-aged males presented significantly higher rates of ≥ five RFs occurrences than females.