Spruance S L, Tyring S K, DeGregorio B, Miller C, Beutner K
Salt Lake City County Health Department, USA.
Arch Intern Med. 1996;156(15):1729-35.
Valaciclovir, the 1-valyl ester of acyclovir, has provided a peroral acyclovir bioavailability 3 to 5 times that of acyclovir itself and is rapidly and completely converted to acyclovir by the liver. Accordingly, valaciclovir has the same antiviral activity as acyclovir, but the potential for enhanced clinical activity and/or less frequent administration because of its superior pharmacokinetics.
We conducted a double-blind, placebocontrolled, patient-initiated clinical trial of peroral valaciclovir, 500 or 1000 mg, or matching placebo tablets twice daily for 5 days for the acute treatment of 1 episode of recurrent herpes genitalis among 987 otherwise healthy volunteers.
Both doses of valaciclovir were equally effective. Patients receiving the lower dose of valaciclovir experienced a median episode length of 4.0 days compared with 5.9 days for those receiving placebo treatment (hazard ratio, 1.9; 95% confidence interval [Cl], 1.6-2.3). Valaciclovir therapy increased the proportion of patients in whom the development of vesicular and ulcerative lesions was prevented in comparison with placebo treatment: 31% vs 21% (relative risk, 1.5; 95% CI, 1.1-1.9). Valaciclovir therapy accelerated the resolution of pain (hazard ratio, 1.8; 95% CI, 1.5-2.1) and the time to cessation of viral shedding (hazard ratio, 2.9; 95% CI, 2.1-3.9). Adverse reactions among the valaciclovir groups were comparable with those of the placebo group.
Valaciclovir therapy provided a clinically significant benefit to patients that included shortening of the duration of lesions, the duration of pain or discomfort, and the duration of virus shedding. In addition, this study, to our knowledge, provides the first convincing demonstration that antiviral therapy can prevent lesion development. These results should prompt a reconsideration of the role that episodic treatment plays in the management of recurrent herpes genitalis.
伐昔洛韦是阿昔洛韦的1-缬氨酸酯，其口服后阿昔洛韦的生物利用度是阿昔洛韦本身的3至5倍，并且能迅速且完全地被肝脏转化为阿昔洛韦。因此，伐昔洛韦具有与阿昔洛韦相同的抗病毒活性，但因其优越的药代动力学特性，具有增强临床活性和/或减少给药频率的潜力。
我们进行了一项双盲、安慰剂对照、患者发起的临床试验，987名健康志愿者口服500毫克或1000毫克伐昔洛韦或匹配的安慰剂片剂，每日两次，持续5天，用于急性治疗复发性生殖器疱疹1次发作。
两种剂量的伐昔洛韦疗效相当。接受较低剂量伐昔洛韦的患者发作持续时间中位数为4.0天，而接受安慰剂治疗的患者为5.9天（风险比，1.9；95%置信区间[CI]，1.6 - 2.3）。与安慰剂治疗相比，伐昔洛韦治疗增加了预防水疱和溃疡性病变发生的患者比例：31%对21%（相对风险，1.5；95% CI，1.1 - 1.9）。伐昔洛韦治疗加速了疼痛的缓解（风险比，1.8；95% CI，1.5 - （此处原文有误，应为2.1））以及病毒脱落停止的时间（风险比，2.9；95% CI，2.1 - 3.9）。伐昔洛韦组的不良反应与安慰剂组相当。
伐昔洛韦治疗为患者带来了临床上显著的益处，包括缩短病变持续时间、疼痛或不适持续时间以及病毒脱落持续时间。此外，据我们所知，本研究首次令人信服地证明抗病毒治疗可预防病变发展。这些结果应促使重新考虑发作性治疗在复发性生殖器疱疹管理中的作用。
