Pharmacokinetics of ganciclovir in a patient undergoing chronic haemodialysis

The pharmacokinetics of ganciclovir was evaluated in a 73-year old anuric, haemodialyzed patient given 1.25 mg·kg^-1 at the end of each haemodialysis session, three times per week.A biexponential decrease in plasma ganciclovir was observed, with a peak concentration of 3.7 mg·1^-1 followed by a steady state value of 2.6 mg·1^-1 for almost 40 h. The total plasma clearance was 0.05 ml·min^-1·kg^-1, the volume of distribution at steady state was 0.61·kg^-1, the elimination half life was 132 h, the area under curve was 372 g·h·ml^-1, the mean residence time was 190 h, and the percentage of ganciclovir cleared from plasma after a 5 h haemodialysis session was 52.1%.The simulated pharmacokinetics over one month, following the same scheme of administration, did not suggest marked accumulation of ganciclovir. These results were obtained after a reduction of 58% in the recommended dose in patients with impaired renal function.     

Liposomally-entrapped ganciclovir for the treatment of cytomegalovirus retinitis in AIDS patients

Treatment of retinitis by cytomegalovirus (CMV) in AIDS patients requires frequent repetitive injections of intravitreal ganciclovir (GCV). This study was undertaken to establish experimentally whether the intravitreal application of liposomally-entrapped GCV could prolong intraocular therapeutic levels when compared with the intravitreal injection of free GCV, and the clinical effectiveness of this approach in AIDS patients. Intraocular concentration of GCV was determined by means of an ELISA test in rabbit vitreous 2, 3, 7, and 14 days after a single intravitreal injection of either different doses of the free drug (0.2–20 mg) or 1 mg of liposomally-entrapped GCV. After 72 h, only the vitreous of rabbits injected with doses of free GCV greater than or equal to 5 mg showed therapeutic levels of the drug; no GCV was detected after 72 h with any of the doses applied. Moreover, the microscopic study revealed GCV-induced damage in retinal structures in the animals injected with a free GCV dose greater than or equal to 15 mg. Intravitreal injection to rabbits of 1 mg of liposomally-encapsulated GCV showed no retinal toxicity at any of the time points studied, and therapeutic levels were detected up to 14 days after injection (4.67 ± 0.39 g/ml). Five AIDS patients suffering CMV retinitis were injected with 0.5 mg of liposomally-entrapped GCV (2 mg of lecithin). Complete remission of the CMV retinitis was observed already at the third injection of 0.5 mg GCV (one per week) and relapse did not occur during the 2–4 month follow-up of the patients. In view of the results presented, it can be concluded that intravitreal injection of liposomally-encapsulated GCV increases the time period required for reinjections in the treatemnt of CMV retinitis.Abbreviations AIDS acquired immunodeficiency syndrome - AZT zidovudine - CMV cytomegalovirus - GCV ganciclovir     

HSV-TK/GCV系统在难治性卵巢癌裸鼠移植瘤模型中的实验研究

目的:建立人难治性卵巢癌荷瘤裸鼠模型,用HSV-TK/GCV自杀基因系统治疗模型动物,观察疗效及协同因素。方法:常规培养携带HSV-TK基因的重组逆转录病毒包装细胞PA317,测定病毒滴度。在移植瘤内多点注射包装细胞,观察GCV、ATRA、TPT对移植肿瘤独立及协同治疗后的肿瘤体积变化。治疗结束后分析移植肿瘤组织病理,PCR检测TK基因在NIH3T3细胞及移植肿瘤组织的转导。结果:人卵巢癌标本裸鼠原代移植成功率16.7%,鼠间传代移植成功率89.7%;重组逆转录病毒滴度为6×104cfu/ml;HSV-TK/GCV系统或TPT治疗后肿瘤生长受到抑制(P<0.05),两者联合治疗后,抑制更明显(P<0.05);ATRA灌胃未显示独立或协同治疗作用(P>0.05);HSV-TK/GCV组、TPT组及两者联合组有明显的治疗反应;PCR检测证实,TK基因在NIH3T3细胞及肿瘤组织中的转导。结论:HSV-TK/GCV系统及TPT对人难治性卵巢癌荷瘤裸鼠有单独及协同治疗作用,全反式维甲酸灌胃对人难治性卵巢癌荷瘤裸鼠疗效不明显。     

更昔洛韦、泛昔洛韦治疗带状疱疹的成本-效果分析

目的 评价更昔洛韦注射剂与泛昔洛韦胶囊治疗带状疱疹构成本及其效果。方法 将符合带状疱疹典型临床症状的门诊患者共84例，随机分为两组，分别给予更昔洛韦注射剂与泛昔洛韦胶囊治疗，副反应评价指标按卫生部1994年不良反应制定标准。结果 更昔洛韦与泛昔洛韦的治愈率分别为86．0％和82．9％，显效率分别为100％和95．1％，但泛昔洛韦的成本效果比明显低于更昔洛韦。结论 泛昔洛韦更具有成本-效果优势。     

更昔洛韦治疗儿童传染性单核细胞增多症临床分析

目的：观察更昔洛韦治疗小儿传染性单核细胞增多症的临床疗效和安全性。方法：将确诊为传染性单核细胞增多症的32例患儿随机分为治疗组16例和对照组16例,对照组给予利巴韦林10~15 mg/（kg·d）静脉滴注,每天1次,治疗组给予更昔洛韦5 mg/（kg·d）静脉滴注,每12 h 1次,两组疗程均为7~10 d,比较两组患儿临床症状消退时间、有效率和不良反应发生情况等。结果：两组发热、咽峡炎、肝脾淋巴结肿大恢复时间比较,治疗组较对照组明显缩短,差异有统计学意义（P〈0.05）;治疗组总有效率93.8%,对照组总有效率75.0%,两组比较差异有统计学意义（P〈0.05）;在治疗观察期间更昔洛韦治疗组未见明显不良反应。结论：更昔洛韦治疗小儿传染性单核细胞增多症可明显缩短热程,减轻症状,安全有效,值得推广。     

更昔洛韦治疗儿童病毒性脑炎疗效评价

目的?总结更昔洛韦治疗儿童病毒性脑炎的疗效。方法: 例病毒性脑炎患儿随机分成治疗组 26 例和对照组 24 例,治疗组 50给予更昔洛韦治疗,对照组给予利巴韦林治疗,对两组疗效进行回顾性分析。结果:治疗组有效率 92.3% ,对照组 70.8% ,治疗组优于对照组( P < 0.01)。结论:更昔洛韦治疗儿童病毒性脑炎安全有效。     

更昔洛韦治疗小儿水痘34例临床观察

目的:探讨更昔洛韦对小儿水痘的临床疗效及安全性。方法:66例水痘患儿随机分为2组,治疗组34例用更昔洛韦注射液5mg/(kg·d),对照组32例用利巴韦林注射液10mg/(kg·d),两组均每日一次静脉滴注,疗程5d,其他治疗方法相同。结果:治疗组热退及结痂时间较对照组缩短(P<0.05),且两组治疗前后周围血白细胞和中性粒细胞比较均无明显差异(P>0.05)。结论:更昔洛韦对小儿水痘有显著疗效,而且安全。     

更昔洛韦治疗婴儿巨细胞病毒性肝炎50例

目的 探讨更昔洛韦治疗婴儿巨细胞病毒性肝炎的治疗效果。方法 对50例确诊巨细胞病毒性肝炎的患儿随机分成对照组和治疗组，均给予保肝等对症处理，另外治疗组加用更昔洛韦，7.5mg/kg,q 12h，连用14d。结果 对照组与治疗组肝功能，黄疸消退差异有显性（P＜0．05）；治疗组婴儿巨细胞病毒性肝炎治愈率80％，与对照组比较差异有非常显性（P＜0．01）。结论 更昔洛韦是治疗婴儿巨细胞病毒性肝炎的有效药物。     

更昔洛韦眼用凝胶治疗复发性单纯疱疹性角膜炎的临床研究

 目的 观察和比较0.15%更昔洛韦眼用凝胶和0.1%阿昔洛韦滴眼液治疗复发性单纯疱疹性角膜炎的疗效和安全性.方法 治疗组30例用更昔洛韦眼用凝胶局部点眼,对照组28例用阿昔洛韦局部点眼,随访12～18个月,平均15个月.结果 治疗有效者治疗组28例,对照组20例,两组间差异有显著意义(P＜0.05).平均治愈天数治疗组(18.12±2.51)少于对照组(21.54±2.38)(P＜0.01).随访期间观察组中随访25例,复发2例,对照组随访15例,复发5例(P＜0.05).结论 更昔洛韦眼用凝胶疗效较阿昔洛韦滴眼液佳,且使用安全.     

Assay of cytomegalovirus susceptibility to ganciclovir in renal and heart transplant recipients

Ganciclovir (GCV) prophylaxis or pre-emptive therapy significantly reduce the rate of cytomegalovirus (CMV) disease and viremia, but increase the potential for emergence of ganciclovir-resistant CMV strains. The inhibitor concentration at 50% (IC(50)) of GCV from 156 CMV isolates from 59 renal or heart transplant recipients was calculated by means of a rapid phenotypic susceptibility assay. Twenty-seven strains were from 14 patients undergoing GCV therapy. The IC(50) was higher in patients under the prophylaxis regimen. One CMV strain, from a heart transplant recipient, became GCV-resistant after 1 month of therapy (IC(50)=13.7 micromol/l). These data, together with clinical and virological markers, suggested that a switch to foscarnet was necessary, and good evolution was observed. Thus, assay of CMV susceptibility to GCV could be helpful in clinical management.