No abstract

Due to its proven clinical effectiveness, lithium has been considered as a corner stone for the long-term treatment of Bipolar Disorder (BPD) for more than half a century. The objective of this study was to evaluate the effect of patients' different co-variables on lithium pharmacokinetics and the development of a pharmacokinetic model for the estimation of lithium clearance in Egyptian bipolar patients; this model can be used afterwards during dosage adjustment to achieve target's steady-state plasma concentrations in similar settings. The study was conducted on 65 adult Egyptian bipolar patients of both genders, in both the in-and outpatient settings in the

Background: Tacrolimus is a widely prescribed immunosuppressant agent for kidney transplantation. However, optimal dosing is challenging due to its narrow therapeutic index, potentially serious adverse effects, and wide inter-individual variability in pharmacokinetics. Cytochrome P450 3A (CPY3A) enzymes metabolize tacrolimus, so allelic variants such as CYP3A4*22 and CYP3A5*3 may contribute to individual differences in pharmacokinetics and therapeutic efficacy of tacrolimus. This study assessed the frequency and influences of CYP3A4*22 and CYP3A5*3 genotypes, alone and combined, on tacrolimus pharmacokinetics and dose requirements in Egyptian kidney transplant patients. Methods: This is a prospective multicenter observational cohort study. Patients were genotyped for the CYP3A4*22 (rs35599367), and CYP3A5*3 (rs776746). Tacrolimus dose (mg), through blood level (ng/ml), and dose-adjusted trough concentration (C0/D) (ng/ml per mg/kg) were recorded during the first and third months posttransplantation and compared among genotype groups. Results: The CYP3A4*22 allele was rare (3.2% of subjects) while the CYP3A5*3 allele was widespread (90.38%) in this cohort. At the third month post-transplantation, median C0/D was significantly higher among CYP3A4*22 carriers than CYP3A4*1/*1 (146.25 [100-380] versus 85.57 [27-370] ng/ml per mg/kg, p = 0.028). Patients harbouring the one copy of the CYP3A4*22 allele and the CYP3A5*3/*3 genotype (n = 5) were classified as poor tacrolimus metabolizers, the CYP3A5*3/*3 plus CYP3A4*1/*1 genotype as intermediate metabolizers (n = 60), and the CYP3A4*1/*1 plus CYP3A5*1/*1 genotype as normal metabolizers (n = 13). During the first month post-transplantation, C0/D was significantly greater in poor metabolizers (113.07 ng/ml per mg/kg) than intermediate and normal metabolizers (90.380 and 49.09 ng/ml per mg/kg) (p < 0.0005). This rank order was also observed during the third month. Acute rejection rate and renal function at discharge did not differ among genotypes. Conclusion: Pharmacogenetics testing for CYP3A4*22 and CYP3A5*3 before renal transplantation may help in the adjustment of tacrolimus starting dose and identify patients at risk of tacrolimus overexposure or underexposure.

: Introduction: Egypt has the highest hepatitis C virus (HCV) seroprevalence in the world mostly caused by HCV genotype 4. The standard of care for chronic hepatitis C (CHC) is a combination of pegylated interferon (INF) and ribavirin (RBV

Background: The purpose of this study was to compare the efficacy and safety of high-dose atorvastatin (40 mg) versus high-dose rosuvastatin (20 mg) in Egyptian patients with type 2 diabetes and previous acute coronary syndrome history. Materials and methods: This open-labeled prospective, randomized clinical trial compared once daily atorvastatin 40 mg (Ator ® ) versus once daily rosuvastatin 20 mg (Crestor ® ). The primary outcome was the 50% reduction in low-density lipoprotein cholesterol levels at 12 weeks. The secondary outcome was the achievement of low-density lipoprotein cholesterol level < 55 mg/dL. Results: A total number of 108 patients had a significant percentage of improvement in atorvastatin arm (n = 59) and rosuvastatin arm (n = 49) in low-density lipoprotein cholesterol, total cholesterol, triglycerides, and high-density lipoprotein-cholesterol achieved (p ≤ 0.05). In atorvastatin arm, 32.2% of patients achieved fifty percent reduction in low-density lipoprotein cholesterol while 34.7% of patients in rosuvastatin arm (p > 0.05). Twenty percent of patients achieved low-density lipoprotein cholesterol < 55 mg/dL in atorvastatin group compared to eighteen percent only in rosuvastatin group (p > 0.05). Regarding safety, the mean difference in liver transaminases was non-significant between the two groups (p > 0.05). Muscular symptoms were experienced by 1.7% patients receiving atorvastatin 40 mg and 10.2% of those receiving rosuvastatin 20 mg (p > 0.05). Conclusions: In Egyptian context, both high doses statin therapy were comparable regarding efficacy and safety in patients with type 2 diabetes and previous history of acute coronary syndrome. The Clinicaltrial.gov registration ID is: NCT05306990.