Plasma and CSF pharmacokinetics of ganciclovir in nonhuman primates

Purpose: The antiviral nucleoside analogue ganciclovir is a potent inhibitor of replication in herpes viruses and is effective against cytomegalovirus infections in immunocompromised patients. Ganciclovir is also used in cancer gene therapy studies that utilize the herpes simplex virus thymidine kinase gene (HSV-TK). The pharmacokinetics of ganciclovir in adults and children have been described previously but there are no detailed studies of the CNS pharmacology of ganciclovir. We studied the pharmacokinetics of ganciclovir in plasma and CSF in a nonhuman primate model that is highly predictive of the CSF penetration of drugs in humans. Methods: Ganciclovir, 10 mg/kg i.v., was administered over 30 min to three animals. Ganciclovir concentrations in plasma and CSF were measured using reverse-phase HPLC. Results: Peak plasma ganciclovir concentrations ranged from 18.3 to 20.0 μg/ml and the mean plasma AUC was 1075 ± 202 μg/ml · min. Disappearance of ganciclovir from the plasma was biexponential with a distribution half-life (t_1/2α) of 18 ± 7 min and an elimination half-life (t_1/2β) of 109 ± 7 min. Total body clearance (Cl_TB) was 9.4 ± 1.6 ml/min/kg. The mean CSF ganciclovir AUC was 168 ± 83 μg/ml · min and the mean peak CSF concentration was 0.7 ± 0.3 μg/ml. The ratio of the AUCs in CSF and plasma was 15.5 ± 7.1%. Conclusions: Ganciclovir penetrates into the CSF following i.v. administration. This finding will be useful in the design of gene therapy trials involving the HSV-TK gene followed by treatment with ganciclovir in CNS or leptomeningeal tumors. Received: 8 May 1998 / Accepted: 25 September 1998     

Cytomegalovirus-related congenital nephrotic syndrome with diffuse mesangial sclerosis

This case report describes congenital nephrotic syndrome in a 2-month-old girl associated with cytomegalovirus infection. Histological examination on renal biopsy showed diffuse mesangial sclerosis and cytomegalic inclusion bodies in the tubular cells and in some glomeruli. Cytomegalovirus (CMV) polymerase chain reaction (PCR) titer in serum was high. Remission of pulmonary and renal symptoms was achieved with ganciclovir in 3 weeks. No recurrence of proteinuria was observed during the follow-up period of 14 months. These finding suggested a causal relationship between congenital nephrotic syndrome and cytomegalovirus infection.     

The risk of cytomegalovirus infection in non-myeloablative peripheral stem cell transplantation compared with conventional bone marrow transplantation

Non-myeloablative allogeneic peripheral stem cell transplantation (NST) is a novel therapeutic strategy for patients with hematologic malignancies. Whether non-myeloablative transplants are associated with increased risk of cytomegalovirus (CMV) infections is unknown. To clarify this issue, we compared the outcome of CMV infection following 24 allogeneic non-myeloablative peripheral blood stem cell transplants and 40 conventional bone marrow transplants (CBT). The NST regimen consisted (mg/kg). Twelve patients (50%) in the NST group and 17 (43%) in the CBT group developed positive antigenemia before day 100 (p=0.60). The time to the first appearance of positive antigenemia was not different between these two groups (p=0.40), and two groups showed similar initial and maximal antigenemia values (p=0.56 and p=0.68, respectively). Only one case of CMV colitis developed in the CBT group whereas CMV disease did not develop in the NST group. Although statistically insignificant, the treatment response against CMV antigenemia using ganciclovir was in favor of NST group. In conclusion, there was no difference in the risk of CMV infection between NST group and CBT group. Further prospective and controlled study is needed to clarify the impact of non-myeloablative procedure on the outcome of CMV infection.     

更昔洛韦治疗新生儿巨细胞病毒感染疗效观察

目的 :探讨更昔洛韦治疗新生儿巨细胞病毒 (HCMV)感染疗效。方法 :将 50例HCMV感染新生儿随机分两组 ,治疗组 2 5例 ,对照组 2 5例。治疗组用更昔洛韦 ,每次 5mg/kg ,每日 2次 ,连用14d。对照组用干扰素 ,每次 1× 10IU ,每日 1次 ,连用 7d。二组均用FQ -PCR法检测血HCMVDNA判断疗效。结果 :更昔洛韦组用FQ -PCR法检测HCMVDNA转阴率 76% ,干扰素组转阴率 4 8% ,X =4 .16(P <0 .0 5) ,具有显著差异。结论 :本组资料表明更昔洛韦治疗新生儿HCMV感染疗效优于干扰素 ,但应注意其可引起白细胞和血小板减低。     

炎琥宁联合更昔洛韦治疗单纯疱疹病毒性角膜炎的临床疗效及对炎症因子的影响

目的 探讨炎琥宁联合更昔洛韦治疗单纯疱疹病毒性角膜炎的临床疗效及对炎症因子的影响.方法 将本院收治的82例单纯疱疹病毒性角膜炎患者按照随机数字表法分为对照组(40例)和观察组(42例),对照组给予阿昔洛韦滴眼液治疗,观察组在阿昔洛韦滴眼液治疗的基础上给予静脉滴注炎琥宁和更昔洛韦治疗.比较两组患者近期临床疗效、不良反应发生率、治疗前和治疗后7、14 d血清及泪液氧化应激指标的差异.结果 观察组临床治疗总有效率为95.24％和平均治愈时间为(15.4±4.6)d,对照组分别为75.00％、(30.5±5.5)d,两组比较差异有统计学意义(P＜0.05);观察组治疗后血清及泪液NO、TAC、MDA、GSH-Px水平改善情况均明显优于对照组(P＜0.05);两组患者治疗期间临床不良反应发生率比较差异无统计学意义(P＞0.05).结论 炎琥宁联合更昔洛韦治疗单纯疱疹病毒性角膜炎的临床效果显著,治愈时间更短,值得临床推广.     

探究更昔洛韦眼用凝胶治疗病毒性角膜炎临床体会

目的分析更昔洛韦眼用凝胶治疗病毒性角膜炎的临床疗效。方法通过选取我院收治的28例,分为2组进行治疗,对比2组患者的临床疗效。结果观察组角膜愈合时间为(4.3±1.1)天,疼痛减轻时间为(3.6±0.8)天,总有效率为92.9%,观察组疗效显著优于对照组(P0.05)。结论使用更昔洛韦眼用凝胶治疗病毒性角膜炎是一种有效的治疗方法。     

更昔洛韦治疗小儿呼吸道合胞病毒肺炎的临床研究

目的：探究更昔洛韦治疗小儿呼吸道合胞病毒肺炎的治疗效果。方法选取2014年1月～2015年1月100例小儿呼吸道合胞病毒的患者，随机分成实验组和对照组。对实验组的患者使用更昔洛韦静脉滴注联合抗病毒治疗，对照组的患者使用炎琥宁静脉滴注联合抗病毒治疗。对比分析两组患者经过治疗后的效果。结果实验组患者经过抗生素联合更昔洛韦治疗小儿呼吸道合胞病毒肺炎较之使用炎琥宁联合抗生素治疗小儿呼吸道合胞病毒肺炎对照组有优势，P＜0.05，差异具有统计学意义。结论更昔洛韦治疗小儿呼吸道合胞病毒肺炎安全、有效、副作用少。     

复方新诺明联合更昔洛韦预防肾移植术后肺部感染

目的 探讨复方新诺明(SMZco)联合更昔洛韦预防肾移植术后早期严重肺部感染的疗效以及不同时期应用SMZco对肾移植受者Scr的影响。 方法 选择我院2005年1月至2006年1月期间肾移植受者240例，分成SMZco联合更昔洛韦预防组(n=84)和单用更昔洛韦预防对照组(n=156)；根据SMZco是否在术后2周内应用将84例SMZco联合更昔洛韦预防组患者分成2周内预防组(n=43)和2周后预防组(n=41)。随访时间至少9个月, 分析SMZco联合更昔洛韦预防对严重肺部感染发生率的影响和抗感染治疗效果以及不同时期应用SMZco对肾移植受者Scr的影响。 结果 SMZco联合更昔洛韦预防组和单用更昔洛韦预防组两组在年龄、性别比例、缺血时间、群体反应性抗体（PRA）水平和补体依赖细胞毒试验（CDC）等方面差异无统计学意义。SMZco联合更昔洛韦预防组严重肺部感染的发生率和感染死亡比例显著低于单用更昔洛韦预防组（2/84比16/156, P = 0.027；0/2比2/16, P < 0.01），但对尿路感染无明显作用。2周内预防组Scr异常发生率远高于2周后预防组（15/43比2/41, P < 0.01）。两组因SMZco引起Scr异常升高者，在停用SMZco 1周内，Scr回到原有正常水平。 结论 肾移植受者口服SMZco联合更昔洛韦预防能明显降低严重肺部感染的发生率和死亡比例。2周后开始口服SMZco预防对Scr影响较小。     

更昔洛韦治疗小儿疱疹性咽峡炎临床分析

目的观察更昔洛韦治疗小儿疱疹性咽峡炎的临床疗效及安全性。方法将106例患儿随机分为两组,治疗组和对照组,治疗组给予更昔洛韦10mg／（kg·d）治疗,对照组给予利巴韦林10mg／（kg·d）治疗,对两组平均退热天数和疱疹消退天数及总有效率进行比较。结果治疗组平均退热天数和疱疹消退天数及总有效率均优于对照组（P〈0．01）。结论更昔洛韦治疗小儿疱疹性咽峡炎安全可靠,疗效显著。     

不同剂量更昔洛韦治疗新生儿先天性巨细胞病毒感染的临床观察

目的：更昔洛韦（GCV）是治疗先天性巨细胞病毒(CMV)感染的首选药物,临床疗效是肯定的,但有一定的副作用。该文旨在评价不同剂量GCV治疗先天性CMV感染新生儿的临床疗效和副作用。方法：先天性CMV感染新生儿167例分为大剂量治疗组（n=79）和小剂量治疗组（n=88）,均给予GCV治疗和其他对症支持治疗。大剂量治疗组给予GCV的剂量为：诱导治疗每次7.5 mg/kg,维持治疗每次10 mg/kg;小剂量治疗组给予GCV的剂量：诱导治疗每次5 mg/kg,维持治疗每次5 mg/kg,观察两组的临床疗效和副作用。结果：①两种剂量的GCV治疗先天性CMV感染有相同疗效,临床症状明显好转,大剂量治疗组CMV IgM转阴率93.8%,CMV DNA转阴率80.8%;小剂量治疗组CMV IgM转阴率93.1%,CMV DNA转阴率为86.7%,两组比较差异无显著性（P>0.05）;②小剂量GCV治疗先天性CMV感染新生儿的副作用低于大剂量GCV,大剂量治疗组呕吐发生率11.4%,贫血发生率20.3%,中性粒细胞减少发生率16.5%,血小板增加发生率18.9%;小剂量治疗组呕吐发生率2.3%,贫血发生率8.0%,中性粒细胞减少发生率5.7%,血小板增加发生率8.0%,两组比较差异有显著性（P<0.05）。结论：小剂量GCV治疗新生儿先天性CMV感染与大剂量有同样的临床疗效,且副作用低于大剂量GCV,更安全,值得临床推广使用。［中国当代儿科杂志,2009,11（8）：641-644］