Utilizing the association between Hepatitis B viral load and Hepatic failure biomarkers for guided antiviral therapy

Background Hepatitis B virus infection is a global public health problem. Individuals with chronic Hepatitis B are at an increased risk of developing liver cirrhosis, hepatic failure and hepato cellular carcinoma. This study was undertaken in a tertiary care hospital with the aim to measure the Hepatitis B viral DNA and its association with hepatic biochemical markersso as to guide for better clinical management during therapy. Methods and Material: Blood samples from 94 Hepatitis B seropositive patients were collected and tested for HBV viral load by real time PCR.Patients were divided in two categories A & B (A= 20000 IU/ml) as based on the quantification of viral DNA. Biochemical tests were performed for assessing Serum ALT, AST, Platelet count, hemoglobin, Albumin, Bilirubin and Prothrombin time. Results: Total patients in category A (20000 IU/ml) were 43.Category B patients with >20000 IU/ml of HBV viral load had elevated levels of SGOT (AST) with statistical significance at P value 0.038. Moreover, Serum albumin and Platelet count were significantly noted on lower side in category B patients at P values 0.03 and 0.02 respectively. Conclusion: Viral load of Hepatitis B varies over time, depending on the phase of theinfection. The findings of this study points at strong correlation between HBV viral load and biochemical markers for hepatic failure.Thus timely and regular viral load monitoring along with hepatic biomarkers is crucial for the treatment of Hepatitis B.

Pharmacokinetic evaluation of differential drug release formulations of rabeprazole in dogs

Objectives: To develop novel dual release prototype capsule formulations of rabeprazole and evaluation of pharmacokinetic properties relative to the reference product (Aciphex®) in Beagle dogs. Methods: The dual release prototype formulations of rabeprazole were developed by preparing optimized mini-tablets core which was subsequently coated with barrier/enteric coating using standard excipients. Both novel prototype formulations were subjected for in vitro release and assay by HPLC-UV to assess long term stability. Single dose pharmacokinetic study used a single sequence three treatments crossover design. In Periods 1 and 2, four dogs received oral 20 mg dose of two prototype formulations. In Period 3, all dogs received a 20 mg oral dose of Aciphex® reference product. There was a 1-week washout time between two successive periods. A quantitative analysis of rabeprazole/sulfide metabolite in plasma samples was performed using a validated LC-MS/MS assay and PK parameters were estimated by non-compartmental analysis. Results: The stability of the prototype formulations was confirmed over a period of 24 months with an acceptable assay and dissolution data. One of the novel prototype formulations showed 70% oral bioavailability relative to the reference product. Despite a 30% reduced bioavailability, this showed 1 h delay in peak concentration, longer plasma residence time of rabeprazole (up to 12 h) and longer apparent elimination half-life. Conclusions: The use of a canine model has enabled the selection of a novel dual-release prototype formulation of rabeprazole for further clinical development.</p