Factors affecting warfarin dose requirements and quality of anticoagulation in adult Egyptian patients: role of gene polymorphism.

BACKGROUND: Warfarin is the mainstay of anticoagulation therapy worldwide. CYP2C9 and VKORC1 are two major genetic factors associated with inter-individual and inter-ethnic variability in the warfarin dose. AIM: This study aims to assess the impact of VKORC1-1639G>A polymorphism and the most common CYP2C9 variant alleles (*2 and *3) on warfarin response in Egyptian patients. METHODS: Genetic analysis of VKORC1-1639G>A and CYP2C9*2, CYP2C9*3 was performed using real-time PCR system. Patients maintained on a constant dose targeting an international normalized ratio range of 2-3.5 for at least three consecutive times were considered as good candidates. A stepwise linear regression analysis was used to determine the independent effects of genetic and non-genetic factors on daily warfarin dose requirements. RESULTS: Patients carrying VKORC1 and CYP2C9 variant genotypes needed a 44.8 % lower mean daily warfarin dose as compared to wild types. Patients with G allele for VKORC1-1639G>A had a significantly higher number of thromboembolic complications per month during therapy. On the first 30 days of therapy, presence of a variant allele either in VKORC1 or in CYP2C9 was associated with increased time required to achieve stable dosing. Multiple regression analysis showed that, VKORC1-1639G>A, age, CYP2C9*3, and smoking status explained 43.4 % of the overall variability in the warfarin dose. CONCLUSION: VKORC1-1639G>A and CYP2C9 polymorphisms contribute to the difference in warfarin dose requirements and quality of anticoagulation amongst Egyptian patients. Study results support using personalized warfarin treatment in Egyptian patients.

Vitamin D levels in Egyptian HCV patients (genotype 4) treated with pegylated interferon.

BACKGROUND/AIM: Vitamin D has been shown to play an important immunomodulatory role. Deficiency of vitamin D has been recently associated to the lack of response to interferon therapy in Hepatitis C virus genotype 1 infected patients. This study aims to evaluate serum level of vitamin D and verify whether circulating vitamin D has any independent role in predicting the rates of HCV virologic response after the administration of pegylated interferon to Egyptian patients infected with genotype 4 HCV. METHODS: Fifty patients infected with HCV genotype 4 and not co-infected with neither Hepatitis B virus nor Human Immunodeffiency Virus were recruited for the study. They were treated with ribavirin-pegylated interferon alpha 2a. Viral titer was determined at baseline, at 12 weeks and at end of treatment (48 weeks). Vitamin D levels and a biochemical profile were obtained for the patients at baseline and at end of treatment. Vitamin D control group consisting of 20 healthy patients of similar age and weight to the study group were recruited to obtain vitamin D levels. RESULTS: Vitamin D levels in HCV infected patients were significantly lower than in healthy subjects. Responders to ribavirin plus pegylated interferon alpha 2a therapy had significantly higher vitamin D levels than non-responders. CONCLUSION: Vitamin D deficiency predicts an unfavorable response to interferon-based treatment of HCV.

Transdermal patch incorporating salbutamol sulphate: In vitro and clinical characterization.

Eudragit patches containing salbutamol sulphate were prepared and evaluated as a rate-controlling membrane for transdermal use. The effect of different Eudragit polymers and various plasticizers on the permeability and mechanical properties of the prepared patches were studied. Drug patches of Eudragit polymers were prepared by a casting method employing methanol as a solvent and dibutylphthalate, polyethylene glycol 400, Propylene glycol, and triacetin as plasticizers. These patches were evaluated for weight and thickness uniformity, swelling index, tensile strength, percentage of elongation, and moisture absorption capacity. In vitro release characteristics of these patches were studied and analyzed. The patches were found to have a uniform thickness. Patches prepared using Eudragit RS 100 (T(8)) as well as RS100 + L100 in a ratio of 3:1 (T(15)) plasticized with triacetin were found to have a tensile strength lower than that of other patches. Permeability characteristics of selected patches were studied. Patch formulations T(8) and T(15) containing 10% oleic acid and 5% dimethyl formamide as penetration enhancers, respectively, displayed the highest permeability to salbutamol sulphate. These two formulations were selected for further clinical investigation and although both resulted in improvement in respiratory function tests, only the first formulation resulted in significant improvement.