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Antiviral treatment is the core part in the treatment of herpes zoster. Based on the latest studies, consensus and guidelines, this article aims to provide a basis and reference for clinicians to make a reasonable choice of types and doses of antiviral agents. Valacyclovir, a precursor of acyclovir with high oral bioavailability and great convenience of administration, is generally the first choice of oral antiviral agents; for some special cases, such as immunocompromised patients, intravenous drips of acyclovir should be selected when appropriate. Brivudine is often a better choice for patients with severe renal insufficiency; famciclovir or other antiviral agents should be considered for patients resistant to acyclovir; for immunocompromised patients resistant to acyclovir, intravenous drips of foscarnet sodium can be an option. Oral antiviral agents should be administered at adequate doses. Selecting appropriate antiviral agents and their doses can effectively relieve acute symptoms of patients and reduce the probability of postherpetic neuralgia.
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@#This article summarizes and analyzes the reported synthetic routes of brivudine in patent and literature.2′-Deoxyuridine was employed as starting material, affording brivudine through iodization, heck coupling, hydrolysis, decarboxylation, bromination and recrystallization.After optimization of reaction conditions of each step, a synthetic route suitable for industrial production was achieved with simple synthetic process, high yield and excellent purity.
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Objective: The current research work focus to simple and rugged bioanalytical method development and validation of brivudine in human plasma using high-performance liquid chromatography. Methods: The analyte (Brivudine) and internal standard (Sofosbuvir) were extracted using the Solid Phase Extraction (SPE) technique. The chromatographic separation was accomplished by using Zorbax eclipse XDB-C18 Column (150×4.6 mm, 5 μm) with a mobile phase consisted of Methanol: 0.5% Ortho-phosphoric acid (65:35%, v/v) respectively, at a flow rate of 0.7 mL/min. The developed method was validated by performing system suitability, carryover effect, linearity, selectivity, sensitivity, precision, accuracy, recovery, ruggedness, and stability studies. The method was validated as per USFDA guidelines. Results: The selected chromatographic condition was found to efficiently separated brivudine (RT-3.55 min) and ISTD (RT-7.87 min). The assay demonstrated a linear dynamic range of 85.205 to 4500.246 ng/ml for brivudine in human plasma with r2>0.99. Demonstrated the lowest limit of detection at 85.205 ng/ml. This method established an intra-run and inter-run precision within the range of 2.99-6.31%CV and 3.67-5.80%CV, respectively. Additional intra-run and inter-run accuracy were within the range of 97.55-105.37% and 99.27-102.15%, respectively. The mean percentage recovery of brivudine and ISTD studies proved good extraction efficiency and the robustness was also evaluated. Conclusion: A simple, accurate, precise, linear and rugged RP-HPLC method was developed and validated for the estimation of brivudine in human plasma with K2EDTA anticoagulant and suitable for conducting BA/BE and TDM.
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OBJECTIVE: To understand the thermal stability, mechanism and kinetics of thermal decomposition of brivudine (BVDU). METHODS: The thermal decomposition process of BVDU was studied by means of thermogravimetry (TG), differential scanning calorimetry (DSC), and thermogravimetric analysis coupled with Fourier transform infrared spectroscopy (TGA-FTIR). The infrared spectra of BVDU, its gaseous products and remainders of thermal decomposition at various temperatures were determined. The molecular bond orders were calculated by GAMESS program of quantum chemistry, and the mechanism of the thermal decomposition of BVDU is discussed. The parameters of thermal decomposition kinetics, such as activation energy Es and pre-exponential factor A, were obtained by using Ozawa method. The prospective lifetime of BVDU was estimated by using Dakin equation. RESULTS: The thermal decomposition of BVDU is a three-stage process. Disconnection of the C-N bond between thymine ring and tetrahydrofuran ring occurrs in the initial step of the decomposition. In nitrogen atmosphere, the average Ea and A of the first stage are 171.1 kJ·mol-1 and 2.630×10 min-1 respectively. In air atmosphere, the corresponding Ea and A are 152.9 kJ·mol-1 and 1.660×10 min-1 respectively. CONCLUSION: The thermal property of BVDU is quite stable in the routine temperature.
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Objective To assess efficacy and safety of oral brivudine 125 mg once daily versus 4 times daily in the treatment of herpes zoster.Methods A five-centre,randomized,double-blind,parallel- controlled study was performed on 226 patients with herpes zoster.Oral brivudine 125 mg was given once daily to 112 patients,and four times daily to 114 patients,both for 7 days.All patients were followed up for 3 weeks after the end of treatment.Results The time to the last formation of new vesicles was 3.88 days for the once daily group,and 3.79 days for the 4 times daily group,without significant differences between the two groups.There was also no significant difference between the two groups with respect to the time to total resolution of vesicles,time to first crusts,time to full crusting,time to first loss of crusts,time to full loss of crusts,time to first relief of pain,and time to complete relief of pain.Postherpetic neuralgia occurred in 34.5% of patients in the once daily group,and 30.4% of patients in the 4 times daily group.The incidence of treatment-related adverse events was 5.4% and 9.6%,in the once daily group and 4 times daily group, respectively.Conclusions Brivudine 125 mg once daily is equally effective,more convenient and safe in comparison with brivudine 125 mg 4 times daily for the treatment of herpes zoster.