Treatment of resistant herpes simplex virus with continuous-infusion acyclovir

Two patients with acquired immunodeficiency syndrome who developed severe ulcerative proctitis caused by herpes simplex virus type 2 that was resistant to acyclovir were successfully treated with 6 weeks of high-dose, continuous-infusion acyclovir sodium (1.5 to 2.0 mg/kg per hour). Viruses cultured from the lesions were resistant to acyclovir in vitro after the patients had received prolonged therapy with oral and intravenous acyclovir in traditional divided doses. Investigation into the mechanism of the acyclovir resistance revealed changes in the thymidine-kinase activity of both isolates. This viral enzyme phosphorylates acyclovir and is necessary for drug activation. The first patient's isolate was deficient of all thymidine-kinase activity, while the second patient's isolate had a thymidine kinase with altered substrate specificity for acyclovir. The continuous infusion was safe, well tolerated, and done in an outpatient setting with weekly clinic visits and monitoring of creatinine and acyclovir levels.     

Oral acyclovir for treatment of first-episode herpes simplex virus proctitis

Twenty-nine patients with first-episode rectal herpes simplex virus infection were enrolled in a double-blind trial of oral acyclovir, 400 mg five times daily, vs placebo treatment. Eighty percent of those receiving acyclovir compared with 25% of placebo recipients no longer had herpes simplex virus isolated from their rectal lesions three days after onset of therapy. The median duration of rectal lesions and viral excretion from rectal lesions (median, five and zero days, respectively) was significantly shorter in patients treated with acyclovir than in placebo-treated patients (14 and 11 days, respectively). Durations of local signs and symptoms of proctitis, such as rectal pain, discharge, and friability, were shorter in acyclovir recipients than in placebo recipients, but these differences were not statistically significant. Daily administration of 2 g of oral acyclovir for ten days alleviates some of the clinical signs of herpes simplex virus rectal infection.     

Double-blind placebo-controlled trial of oral acyclovir in first-episode genital herpes simplex virus infection

One hundred nineteen patients with primary and 31 patients with nonprimary first-episode genital herpes were treated for ten days with 200 mg of acyclovir capsules or placebo capsules orally five times daily. Among acyclovir recipients with primary genital herpes, the median duration of viral shedding (two days), time to crusting of all lesions (seven days), time to healing of all lesions (12 days), and duration of local pain (five days) and constitutional symptoms (three days) were shorter than among placebo recipients (9, 10, 16, 7, and 6 days, respectively). Among patients with nonprimary first-episode genital herpes, oral acyclovir shortened the median duration of viral shedding but had no significant effect on the duration of lesions or symptoms. The time to first recurrence and frequency of recurrences were similar in acyclovir- and placebo-treated patients. Oral acyclovir treatment of primary first-episode genital herpes shortens the duration of viral shedding and symptoms and accelerates healing, but it does not appear to influence subsequent genital recurrences.     

Long-term acyclovir suppression of frequently recurring genital herpes simplex virus infection. A multicenter double-blind trial

Normal adults with six or more episodes of genital herpes in the previous year were enrolled in a one-year, multicenter, double-blind trial comparing placebo with 400 mg of acyclovir administered orally twice daily. Patients with episodes during the study were offered 200 mg of acyclovir administered orally five times daily for five days; this allowed comparison of suppressive and episodic treatment. After one year, 227 (44%) of 519 patients receiving suppressive treatment and seven (2%) of 431 receiving placebo (episodic) treatment remained free of recurrences, and the mean numbers of recurrences per year were 1.8 and 11.4, respectively. Among 67 patients who had received suppressive therapy for one year, the mean duration of lesions in the first episode following the discontinuation of treatment was 9.3 days compared with 7.3 days among 45 patients who had received episodic therapy for one year. Treatment was well tolerated, and no changes were noted in the in vitro susceptibility to acyclovir of herpes simplex virus cultured during or after the one-year trial. Continuous or episodic oral acyclovir therapy for one year remained safe and effective.     

阿昔洛韦葡萄糖注射液的毒性研究

目的:观察阿昔洛韦葡萄糖注射液的用药安全性。方法:采用静脉血管刺激实验、过敏实验和溶血实验,检测阿昔洛韦葡萄糖注射液是否存在毒性反应。结果:实验表明该药对家兔耳缘静脉无明显刺激作用,也不引起过敏反应和溶血。结论:阿昔洛韦葡萄糖注射液无明显毒副作用,具有临床用药的安全性。     

阿昔洛韦琥珀酰亚胺活性酯的制备研究

目的 合成阿昔洛韦琥珀酰亚胺活性酯.方法 以阿昔洛韦为起始原料,在二甲基甲酰铵(DMF)为溶媒及三乙胺的碱性条件下,与丁二酸酐反应生成阿昔洛韦衍生物9-(2-丁二酸单酰乙氧基甲基)鸟嘌呤(SACV),再与N-羟基琥珀酸亚胺在N,N-二环己基碳化亚胺的存在条件下合成阿昔洛韦琥珀酰亚胺活性酯.结果 与结论合成产物产率为79.1%,mp为125～126 ℃,其结构经IR和NMR确证,所得化合物为一新化合物.     

阿昔洛韦片在健康志愿者体内的相对生物利用度

目的:研究阿昔洛韦片的相对生物利用度.方法:采用标准二阶段交叉设计自身对照试验方法,应用反相高效液相色谱法测定20名健康自愿受试者单剂量口服400 mg阿昔洛韦片后,阿昔洛韦血药浓度变化情况,经3p97药动学程序处理.结果:药-时曲线下面积分别为(4.67±1.01) (μg·h)/L和(4.67±1.19) (μg·h)/L,达峰时间分别为(1.80±0.48) h和(1.75±0.49) h,峰浓度分别为(1.13±0.13)μg/L与(1.12±0.18)μg/L.配对t检验与双单侧t检验结果表明,二者药-时曲线下面积、峰浓度及达峰时间均无显着性差异(P>0.05).阿昔洛韦片供试品的相对生物利用度为101.3%.结论:阿昔洛韦片供试品与标准参比制剂为生物等效制剂.     

Prolonged continuous acyclovir treatment of normal adults with frequently recurring genital herpes simplex virus infection. The Acyclovir Study Group

In this 3-year study of suppressive acyclovir for recurrent genital herpes, patients with more than six recurrences per year were randomized initially to 400 mg of acyclovir or placebo orally two times per day, with recurrences treated with 200 mg of acyclovir five times per day for 5 days. In the second year of the study, all patients received acyclovir as a daily suppressive or intermittent acute therapy; in the third year, all received daily acyclovir. Among 525 patients completing 3 study years, 289 received 3 years of suppressive therapy and 236 received 1 year of acute therapy followed by 2 years of suppressive therapy. Of those who completed the third year, 61% were recurrence free that year; 25% of the suppressive therapy-only group were recurrence free for all 3 years. The annual recurrence rate dropped from more than 12 recurrences per year at baseline to 1.0 (suppressive therapy) and 1.4 (acute and suppressive therapy) recurrences during the third year. No significant toxic effects were detected. Daily suppressive acyclovir therapy was effective and well tolerated.     

热毒宁注射剂与阿昔洛韦配伍的稳定性研究

目的 探索热毒宁注射液与阿昔洛韦配伍的稳定性。方法 在室温25 ℃观察两种药物混合液在60 min内的外观、pH值、光谱图变化。结果 两种药物较高浓度混合液会立即出现浑浊和颜色改变,较低浓度混合液的外观清澈透明、微黄;低浓度混合液60 min内的pH值稳定;各时间点的吸光度值显著下降,质量分数明显减少。结论 热毒宁注射液与阿昔洛韦无论浓度高低均存在配伍禁忌,建议避免混合应用。     

Successful treatment of herpes labialis with topical acyclovir

A double blind, placebo controlled trial of 5% acyclovir cream, applied topically five times a day for five days, was carried out in 49 patients with recurrent herpes labialis. These patients had a total of 74 episodes, 34 of which were treated with the 5% acyclovir cream and 40 with matching placebo. First episodes and all episodes treated with acyclovir cream had significantly shorter times to formation of ulcer or crust and to complete healing (p less than 0.05 for all variables). The duration of all symptoms and proportion of patients developing itching was also reduced by acyclovir cream in first episodes, though the difference was not significant. When the patient started treatment early in the course of a first episode acyclovir cream significantly reduced the percentage of lesions progressing beyond the papular stage (p less than 0.05). Acyclovir cream is well tolerated and effective for the treatment of recurrent herpes labialis.     

槲皮素对小肠吸收阿昔洛韦的促进作用

目的: 研究槲皮素抑制P-糖蛋白(P-Glycoprotein P-gp)对小肠吸收阿昔洛韦的影响.方法: 采用小肠翻转实验和离体小肠吸收实验考察槲皮素促进阿昔洛韦的吸收.结果:小肠翻转实验结果表明,经不同浓度的槲皮素溶液孵育后,阿昔洛韦由小肠黏膜侧到浆膜侧的转运量随槲皮素浓度的增加而增加,经拟合符合Boltzmann 方程;离体小肠吸收实验结果表明,经不同浓度的槲皮素溶液孵育后,阿昔洛韦由小肠浆膜侧到黏膜侧的转运量随槲皮素浓度的增加而减少.结论:槲皮素为P-gp抑制剂,其多药耐药逆转作用有利于促进阿昔洛韦的吸收.     

6-O-取代阿昔洛韦衍生物的合成及其抗病毒活性

目的:通过对阿昔洛韦分子中碱基的结构修饰,设计并合成6-O-取代阿昔洛韦衍生物,并初步测定它们的抗病毒活性.方法:以阿昔洛韦为先导化合物,合成一系列6-O-取代阿昔洛韦衍生物,并以阿昔洛韦为阳性对照对猴肾细胞Vero进行体外抗HSV-Ⅰ和HSV-Ⅱ病毒活性测定.结果:合成了6-O-取代阿昔洛韦衍生物10个,结构均经过元素分析或MS确认.部分目标化合物具有一定的体外抗HSV-Ⅰ和HSV-Ⅱ病毒活性(MIC分别为25、50 ng·L-1),但较阿昔洛韦(MIC为2 ng·L-1)作用弱.结论:所合成的目标化合物虽然可能在体内更易于吸收,但体外初步抗病毒活性实验结果表明作用较弱.     

HPLC法测定阿昔洛韦片中阿昔洛韦的含量

目的：建立阿昔洛韦片中阿昔洛韦的含量测定方法。方法：采用高效液相色谱法，以十八烷基硅烷键合硅胶为填充剂，色谱柱为HypersilC18柱（4．6mm×200mm，5μm）；流动相为甲醇-水（10：90）；流速1．0ml／min；检测波长254nm；柱温：室温；进样量20μl。按外标法以峰面积计算阿昔洛韦含量（以标示量的百分含量表示）。结果：阿昔洛韦浓度在5-30μg／ml范围内与峰面积呈良好的线性关系；平均回收率为100．00％，RSD=0.22％；三批样品的平均含量是98．9％，RSD=0．20％。结论：本方法专属性强、灵敏度高、重现性好，可用于阿昔洛韦的含量测定。