Brivudine is an analog of thymidine, and is incorporated into the viral DNA. It blocks the action of DNA polymerases, thus inhibiting viral replication. It has a stronger antiviral effect against the varicella-zoster virus compared with reference compounds such as aciclovir or penciclovir[3]. It has high, selective activity against varicella zoster virus (VZV), inhibiting VZV replication, possibly through competitive inhibition of viral DNA polymerase, or by acting as an alternative substrate to deoxythymidine triphosphate, causing viral DNA strand breakage. Oral brivudin is generally well tolerated, with a similar tolerability profile to those of oral acyclovir or famciclovir. Nausea was the most commonly reported adverse event[4]. As opposed to the others, brivudine is a non-nephrotoxic drug that should not be administered to immunodepressed patients or to those being treated with 5-fluorouracil[5].
(E)-5-(2-Bromovinyl)-2'-deoxyuridine/溴夫定 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Vero cells
0.3, 0.6, 1.3 μM
24 h
To investigate the effect of BVdU on the synthesis of HSV-1-specific polypeptides, showing marked alterations in the synthesis and processing of HSV-1-infected cell polypeptides.
To study the inhibitory effect of BVdUrd on EBV DNA polymerase, results showed that EBV DNA polymerase was less sensitive to BVdUrd.
Proc Natl Acad Sci U S A. 1981 May;78(5):2698-702
HSV-1 infected KB cells
0.007-0.01 μg/ml
To study the inhibitory effect of BVdUrd on HSV-1 replication, results showed that BVdUrd could inhibit HSV-1 replication at very low concentrations.
Proc Natl Acad Sci U S A. 1981 May;78(5):2698-702
Vero cells
0.5 μg/ml
7 days
To evaluate the inhibitory effect of BVdU on HSV-1 and HSV-2, it was found that the titers of HSV-1 were reduced by more than 3 log10, while the titers of HSV-2 were reduced by less than 2 log10.
J Clin Microbiol. 1985 Mar;21(3):459-61
Vero cells
10 μg/ml
8 h
To investigate the metabolic differences of BVdU in HSV-1 and HSV-2 infected cells. Results showed that HSV-1 infected cells metabolized BVdU to triphosphate (BVdUTP), while HSV-2 infected cells only metabolized it to monophosphate (BVdUMP).
Antimicrob Agents Chemother. 1984 Nov;26(5):762-5
P3HR-1(LS) cells
0.055 μM
14 days
Evaluate the inhibitory effect of BVdU on EBV DNA replication. Results showed an ED50 of 0.055 μM and a therapeutic index of 6,500.
Evaluate the inhibitory effect of BVDU on varicella-zoster virus (VZV) replication. Results showed that BVDU significantly inhibited VZV replication at very low concentrations without significant toxicity to host cells.
Antimicrob Agents Chemother. 1982 Jan;21(1):33-8
(E)-5-(2-Bromovinyl)-2'-deoxyuridine/溴夫定 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Wistar rats
Wistar rats
Intraperitoneal injection
90μmol/rat
Single dose
To study the metabolism and regeneration of BVdUrd in vivo. Results showed that BVdUrd was cleared from the bloodstream within 2-3 hours after injection, degraded to BVUra, which remained in the bloodstream for a longer time. BVdUrd could be regenerated from BVUra by injecting dThd or other 5-substituted deoxyuridines.
Nucleic Acids Res. 1984 Feb 24;12(4):2081-90
NMRI mice
20-day-old mice weighing approximately 10 to 12 g
Intraperitoneal, subcutaneous, or oral route
100 mg/kg
Single dose, samples taken at 20, 40, 80, 160, or 320 minutes after administration
Compared the pharmacokinetics of (E)-5-(2-bromovinyl)-2'-deoxyuridine with 5-iodo-2'-deoxyuridine, found that the active drug concentrations of (E)-5-(2-bromovinyl)-2'-deoxyuridine in serum were significantly higher than those of 5-iodo-2'-deoxyuridine, and active drug levels could still be detected 320 minutes after oral administration
Antimicrob Agents Chemother. 1979 Aug;16(2):234-6
Rabbits
Experimental herpes simplex keratoconjunctivitis
Topical application
0.5% ointment
Five times a day for 5 consecutive days
Compare the effectiveness of BVDU and IDU in preventing and treating experimental herpes simplex keratoconjunctivitis. Results showed BVDU was significantly better than IDU in suppressing conjunctivitis and promoting healing of keratitis.
Antimicrob Agents Chemother. 1980 Jan;17(1):8-12
Hairless (hr/hr) mice
Cutaneous herpes simplex virus type 1 (HSV-1) infection model
Topical application
0.3%, 1%, 3%, 10%
Four times a day for 5 days
Suppressed the development of herpetic skin lesions and reduced the associated paralysis and mortality. BVdU was effective even at a concentration as low as 0.3% in 5% Azone-DMSO.
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