Therapeutic drug monitoring (TDM) is increasingly recommended in antiepileptic drug (AED) therapy, yet a complex relationship exists between the unbound-drug serum concentration (C u.serum ) as a monitoring biomarker and clinical efficacy. The study was designed to investigate the validity of the intracellular unbounddrug concentration in Peripheral Blood Mononuclear Cells (C u.PBMC ) as a feasible TDM tool in relation to levetiracetam (LEV). Methods: Patients from epilepsy out-patient centre were included in a 4-month descriptive prospective study. Trough serum and PBMC LEV concentrations were monthly determined using HPLC and correlated with clinical features, demographic data, and P-glycoprotein (P-gp) expression. Results: Seventy-patients completed the study with a LEV dose range of 500−3000 mg/day. An absolute range for LEV C u.serum and C u.PBMC was 1.00-26.99 and 0.33-4.43 μg/mL, respectively. Unlike C u.serum , the average four-month LEV C u.PBMC displayed a significant positive correlation with clinical features and P-gp expression; where patients with higher LEV C u.PBMC experienced less number of seizure/month, better cognition and quality of life, and had a more reduction in P-gp expression, but no significant correlation with LEV daily dose was observed. A therapeutic response threshold of ≥ 0.82 μg/mL for LEV C u.PBMC was perceived by using a receiver operating characteristic curve that related the number of seizure/month to the LEV C u.PBMC . The validity of this therapeutic threshold was significant in contrast to LEV Cu.serum. Conclusion:Levetiracetam PBMC concentration is a more sensitive biomarker for LEV efficacy and correlates better with clinical events than C u.serum and could represent a novel tool for more precise LEV monitoring.

Blood–brain barrier (BBB) efflux transporters' overexpression hinders antiepileptic drug brain entry. Breast cancer resistance protein (BCRP) is a major BBB efflux transporter. In the present work, BCRP's role as a mechanism that might contribute to drug-resistant epilepsy (DRE) in a mouse model of acute seizures was studied with further assessment of the effect of its inhibition by ko143 and metformin (MET) on lamotrigine (LTG) bioavailability and efficacy. 42 male mice divided into 6 groups: G1: Normal control, G2: LTG-injected healthy mice: LTG 20 mg/kg i.p., G3: Acute seizures (A.S) mice: Pentylenetetrazole (PTZ) 50 mg/kg i.p., G4: LTG-treated A.S mice: LTG 20 mg/kg + PTZ 50 mg/kg i.p., G5: Ko143 + LTG treated A.S mice: Ko143 15 mg/kg i.p. before LTG + PTZ, G6: MET + LTG treated A.S mice: MET 200 mg/kg i.p. before LTG + PTZ. Seizures severity, serum, brain LTG, and brain BCRP were assessed. PTZ group experienced the highest seizure frequency and brain BCRP expression. Ko143 and MET groups showed a significant decrease in brain BCRP with subsequent improvement in brain LTG level and better seizure control. BCRP has a significant role in epilepsy resistance and its inhibition with ko143 or MET adds value to DRE management.

The effectiveness of a website to enhance knowledge and skills of Adobe Photoshop program for the design of women's leather goods Citation: Shimaa Abdelfatah et al. (2022), The effectiveness of a website to enhance knowledge and skills of Adobe Photoshop program for the design of women's leather goods,

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