Advances in the antiviral therapy of herpes virus infection in children

Herpes viruses are ubiquitous, and primary infection with many of these viruses is common during childhood. In general, children tolerate primary infection well, with only mild symptoms, but in the immunocompromised, including the newborn, infection can be associated with serious morbidity and mortality. Drug treatment for many of the herpes infections is available but is often associated with serious side effects. In the pediatric age group, treatment is further hindered by a lack of information on suitable dosing regimes, unavailability of oral solutions and a lack of clinical trials specifically investigating response to treatment in this group of patients. This article will review current evidence regarding the pharmacokinetics and dosing of the most commonly used antiherpetic agents and will look specifically at the treatment of the more common herpes virus infections in children.     

梯度洗脱HPLC法测定人血浆中阿昔洛韦的浓度

目的:建立一种快速、灵敏、准确的高效液相色谱测定人血浆中阿昔洛韦浓度的方法。方法:以硫酸沙丁胺醇为内标,采用Shimadzu LC-10AD液相色谱仪,以Shimadzu C_(18)为分析柱(100mm×3mm,3μm),柱温35℃;流动相采用梯度洗脱法,A泵为乙腈,B泵为0.1mol·L~(-1)磷酸溶液,流速为A泵:0.005mL·min~(-1),B泵0.600mL·min~(-1);进样量20μL;荧光检测器:Ex=285nm,Em=370nm。结果:色谱峰分离良好,无干扰。测定数据进行回归,线性方程为:Y=0.001604X+0.02230,r=0.9997。检测范围:20～1500ng·mL~(-1)。结论:本法是一种可靠的、快速灵敏的检测方法,适用于包含阿昔洛韦前体药物的药动学的研究。     

The role of stratum corneum and dermal microvascular perfusion in penetration and tissue levels of water-soluble drugs investigated by microdialysis

BACKGROUND: Hydrophilic drugs are poorly absorbed when applied topically, due to low partitioning through the lipid matrix of the stratum corneum. Cutaneous blood flow rapidly clears the absorbed drug, which may result in low tissue levels. This is of importance for topically applied drugs whose site of action is within the epidermis or dermis. Dermal drug levels can be measured using cutaneous microdialysis, which is a means of continuously sampling substances from the dermal extracellular fluid. OBJECTIVES: To measure the contribution of stratum corneum barrier and microvascular perfusion in determining dermal tissue levels of hydrophilic drugs (aciclovir and penciclovir) in vivo. METHODS: Studies were performed using microdialysis of the volar surface of the forearm of healthy volunteers (n = 55) over a 5-h collection period. Stratum corneum was removed by tape stripping, and barrier disruption quantified by measurement of transepidermal water loss (TEWL); dermal microvascular perfusion was modulated by inclusion of noradrenaline in the microdialysis perfusate. RESULTS: With intact skin and normal cutaneous blood flow the concentration of penciclovir recovered was below assay threshold (0.05 ng x mL(-1). With noradrenaline-induced local vasoconstriction, the area under the curve of drug absorbed through normal skin (+/- SEM) was 13.3 +/- 2.9 ng mL(-1) h(0-5) for penciclovir and 27.6 +/- 10.6 ng mL(-1) h(0-5) for aciclovir. Removal of the stratum corneum (to glistening) by tape stripping increased penciclovir absorption by 1300-fold and aciclovir absorption by 440-fold, confirming the stratum corneum as the major barrier to hydrophilic drug absorption. Sequential barrier disruption by tape stripping gave a close correlation between penciclovir concentration absorbed per hour and barrier disruption measured by TEWL (r2 = 0.9283). There was a 15.6-fold difference in the recovery of penciclovir through barrier-deficient skin with and without cutaneous blood flow. There was no relationship between fibre depth and amount of drug dialysed, which suggests free movement of antiviral drug on reaching the aqueous environment of the dermis. CONCLUSIONS: This study defines for the first time the relationship between the degree of mechanical barrier impairment and drug absorption at the same anatomical site in humans, and the role of blood flow in drug clearance in vivo.     

喷昔洛韦乳膏治疗生殖器疱疹临床观察

目的　评价喷昔洛韦乳膏治疗生殖器疱疹的疗效和安全性。方法　将 94例生殖器疱疹的患者随机分为治疗组外用喷昔洛韦乳膏涂患处 4～ 5次 /d ,和对照组阿昔洛韦软膏涂患处 4～ 5次 /d进行比较。结果　治疗组与对照组在有效率和痊愈率上有显著性差异 (P <0 .0 5 )。结论　喷昔洛韦乳膏是治疗生殖器疱疹安全有效的药物     

抗病毒药阿昔洛韦的合成

从鸟嘌呤核苷为起始原料,经三步反应制得高效抗病毒药阿昔洛韦,总收率52%。     

盐酸伐昔洛韦片的药动学及相对生物利用度

目的:研究盐酸伐昔洛韦片在健康人体的药动学和相对生物利用度。方法:采用两制剂双周期交叉对照的研究方法,以HPLC法测定18例健康志愿者单剂量口服盐酸伐昔洛韦片600mg后血浆中阿昔洛韦的浓度变化,采用DAS2.0软件计算药动学参数。结果:阿昔洛韦的线性范围为0.201～12.884mg.L-1(r=0.9999),日内和日间RSD均小于6.0%。供试制剂与参比制剂的主要药动学参数tmax分别为(1.5±0.6)h和(1.9±0.7)h;Cmax分别为(2.7±0.5)mg.L-1和(2.8±0.7)mg.L-1;t1/2分别为(3.0±0.6)h和(3.3±0.9)h;AUC0-t分别为(10.6±1.9).和(10.6±2.4)mg.L-1.h;AUC0-∞分别为(11.5±2.0)mg.L-1.h-1和(11.7±2.6)mg.L-1.h。两种盐酸伐昔洛韦片主要药动学参数间差异均无显著性(P>0.05)。供试制剂对参比制剂的相对生物利用度为(101.9±14.9)%。结论:供试制剂和参比制剂具有生物等效性。     

荷转移分光光度法测定注射用阿昔洛韦的含量

目的:电荷转移分光光度法测定注射用阿昔洛韦的含量。方法:电荷转移分光光度法。阿昔洛韦作为电子给体,对硝基苯酚作为电子受体,两者反应生成荷转移化合物。结果:阿昔洛韦与对硝基苯酚形成荷转移化合物的表观百分吸收系数为(503.5±20.0),测定阿昔洛韦的线性范围为10~100mg.L-1,精密度RSD为0.9%,检测限为0.3mg.L-1,回收率为(99.6±1.2)%。结论:阿昔洛韦与对硝基苯酚形成荷转移化合物稳定,可用于测定注射用阿昔洛韦的含量。     

阿昔洛韦温敏凝胶的制备及评价

目的制备阿昔洛韦温敏凝胶,对其理化特性和使用效果进行初步评价。方法以泊洛沙姆407为凝胶基质,制备阿昔洛韦温敏凝胶剂。采用试管倒置法研究相变行为。采用紫外分光光度法测定含量,采用Franz扩散池法考察体外释药行为,家兔皮肤局部使用初步评价胶凝效果和刺激性。结果制得阿昔洛韦温敏凝胶外观均一透明,胶凝温度约27℃,相变可逆,含主药(2.86±0.02)%,体外缓释6 h,符合一级释药特性。家兔皮肤局部使用证明其分散性良好,胶凝时间为(10±1)s,药物滞留量约为溶液剂的6倍,且无皮肤刺激性。结论制得阿昔洛韦温敏凝胶剂,质量评价结果良好。     

高效液相色谱法测定阿昔洛韦滴眼液的含量

目的：采用HPLC测定阿昔洛韦滴眼液的含量。方法：流动相为甲醇-水（40：60）,检测波长为254nm。结果：阿昔洛韦浓度在6-32ug.ml^-1范围内线性关系良好。r=0.9992,平均回收率为100.8%,RSD为1.0%(n=5)。结论：方法简便,结果可靠。     

阿昔洛韦分散片的HPLC法测定

采用离子对高效液相色谱法测定阿昔洛韦分散片含量.线性范围为1－20－μg/ml,r=0.9999,平均回收率为100．0％,RSD为1．2％。