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Antimicrobials during Pregnancy
Published in “Bert” Bertis Britt Little, Drugs and Pregnancy, 2022
Vidarabine is a DNA inhibitor used systemically to treat disseminated herpes simplex infections and locally to treat herpetic ophthalmic infections. There are no adequate human studies available. However, Schardein et al. (1977) and Kurtz and associates (1977) reported congenital anomalies in rats given several times the usual human dose. Hillard and colleagues (1982) reported on the use of this drug late in pregnancy for disseminated herpes simplex infections.
High-Performance Liquid Chromatography
Published in Adorjan Aszalos, Modern Analysis of Antibiotics, 2020
Joel J. Kirschbaum, Adorjan Aszalos
Bulk vidarabine was assayed using an octadecylsilane column and a mobile phase consisting of 2.2 g sodium docusate in 10 ml glacial acetic acid, plus 500 ml methanol, which is finally diluted to 1 liter with water. Detection was at 254 nm [134]. Vidarabine and its metabolite, arabinosylhypoxanthine, were assayed in biological fluids using a 5-μm octylsilane column at 40°C, with a mobile phase of 0.005 M sodium pentanesulfonate buffer, pH 7.2-acetonitrile (20:480) flowing at 1 ml/min through a detector set to 250 nm [135]. The limit of detection is 0.5 μg/ml in serum and cerebrospinal fluid and 2.5 μg/ml in urine.
Antiviral therapeutics for viral infections of the central nervous system
Published in Avindra Nath, Joseph R. Berger, Clinical Neurovirology, 2020
If untreated, HSE mortality approaches 70%, and of those patients who do survive, significant neurologic morbidity occurs in nearly 97% [10]. Idoxuridine was the first antiviral agent studied clinically in HSE, but was found to be both ineffective and toxic [11]. Vidarabine was shown to be more tolerable than idoxuridine and to reduce HSE mortality to 54%, but 86% of survivors suffered neurologic impairment. Acyclovir dosed at 30 mg/kg/day given in 3 divided doses further improved mortality and morbidity, as evidenced by 28% mortality and 62% of survivors having some form of neurologic debility, conversely 38% were reported as having returned to usual function one year later [12]. This clinical trial also showed that patients with HSE who are over 30 years of age or have a lower level of consciousness (Glasgow Coma Scale of 6 or less) prior to initiation of treatment are at greater risk for a poor therapeutic outcome. Acyclovir is currently the standard of care for treatment of all HSV infections of the CNS, including HSE.
Advances in biocatalytic and chemoenzymatic synthesis of nucleoside analogues
Published in Expert Opinion on Drug Discovery, 2022
Sebastian C. Cosgrove, Gavin J. Miller
Tamborini, Ubiali, and colleagues also presented a recent flow synthesis of the nucleoside analogue vidarabine [42]. Using the AhPNP described above (Section 2.4) in concert with the uridine phosphorylase from Clostridium perfringens (CpUP), they tested immobilization on two different supports: a glyoxyl-functionalized agarose via condensation with surface amino groups, and EziG (a porous glass-resin which contains iron centers for coordination) via affinity binding of histidine-tagged proteins. In this instance, the EziG was found to be a much more effective support. Both enzymes had a 97% immobilization yield (the amount of enzyme immobilized from solution), whereas with the glyoxyl support the yield was only 40% for CpUP (100% for AhPNP). The recovered activity was better for both enzymes on EziG (14% vs 22% for CpUP, and 35% vs 52% for AhPNP). In practice, the enzymes were packed into a column (3 mL column volume) and run continuously (120 minute residence time) for 8 days. After this, they precipitated 1.1 g of vidarabine from the effluent in a 55% isolated yield.
Metabolomic tools used in marine natural product drug discovery
Published in Expert Opinion on Drug Discovery, 2020
Kevin Andrew Stuart, Keira Welsh, Molly Clare Walker, RuAngelie Edrada-Ebel
The first marine-derived drug to be approved was Cytosar-U® (cytarabine) in 1969 for the treatment of non-Hodgkin’s lymphoma and meningeal leukemia; followed by Vira-A® (vidarabine) in 1976 as an antiviral, prescribed against herpes, pox, and some rhabdoviruses [2]. Cytarabine and vidarabine are synthetic nucleosides developed from isolates of the sponge Tethya crypta [3]. The mechanism of action of cytarabine is not yet fully understood, though it appears to be intracellularly converted to its active form cytarabine triphosphate, which competes with deoxycytidine triphosphate as a substrate for DNA polymerase, inhibiting DNA synthesis [2]. Vidarabine has a higher toxicity and is less stable than more popular antiviral agents, and exhibits a low oral bioavailability and poor solubility [4], which contributed to its withdrawal from use in the US in 2001 [2]. Cytarabine remains a staple in cancer therapy today [2].
Herpes Zoster Ophthalmicus with Orbital Apex Syndrome—Difference in Outcomes and Literature Review
Published in Ocular Immunology and Inflammation, 2018
Jie Jie Lim, Yu Ming Ong, M. Zain Wan Zalina, May May Choo
While the optimal therapy for OAS secondary to HZO remains unclear, the current mainstay of treatment is combined administration of systemic acyclovir and steroids.5,15 In the reported cases, most of the cases showed good improvement in response to the treatment with systemic acyclovir and steroids. One of the reported cases was treated with vidarabine due to compromised renal function. She also achieved good vision at the end of the treatment. Three of these patients did not achieve good vision despite treatment with systemic antivirals and steroids. The poor vision for the three reported cases was all attributed to optic atrophy.