Garré B, Gryspeerdt A, Croubels S, De Backer P, Nauwynck H
Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
Vet Microbiol. 2009 Mar 30;135(3-4):214-21. doi: 10.1016/j.vetmic.2008.09.062. Epub 2008 Sep 21.
The purpose of the current study was to investigate the therapeutic efficacy of valacyclovir against EHV1 in a controlled study. Eight naïve Shetland ponies were inoculated with 10(6.5) TCID(50) of the neuropathogenic strain 03P37. Four ponies were treated with valacyclovir at a dosage of 40mg/kg bodyweight, 3 times daily, for 5 (n=2) or 7 (n=2) consecutive days, while the other four ponies served as untreated controls. The treatment regimen started 1h before inoculation. Ponies were monitored daily for clinical signs. At 0, 1, 2, 3, 4, 5, 7, 9, 11, 14, 17 and 21 days post inoculation (d pi), a nasopharyngeal mucus sample was taken to determine viral shedding. At the same time points, blood was collected and peripheral blood mononuclear cells (PBMC) were isolated to determine viremia. During the treatment, blood samples were collected 6 times daily, i.e. just before valacyclovir administration and 1h later, to determine the concentration of acyclovir in plasma. Also a nasopharyngeal swab was taken to measure the acyclovir concentration in nasal secretion. No differences could be noticed between valacyclovir-treated and untreated ponies. The clinical signs, the viral shedding and the viremia were similar in both the groups. Plasma acyclovir concentration could be maintained above the EC(50)-value of EHV1 during 50% of the entire treatment period in valacyclovir-treated ponies. Acyclovir could be detected in nasal swabs at concentrations varying from 50% to 100% of the corresponding plasma concentration. Although sufficiently high acyclovir levels could be reached in plasma and nasal mucus, no effect was seen of the treatment with valacyclovir on clinical signs, viral shedding and viremia of EHV1-infected ponies.
本研究的目的是在一项对照研究中调查伐昔洛韦对马疱疹病毒1型(EHV1)的治疗效果。八匹未接触过该病毒的设得兰矮种马接种了10(6.5)半数组织培养感染剂量(TCID(50))的神经致病性03P37毒株。四匹矮种马以40mg/kg体重的剂量接受伐昔洛韦治疗,每日3次,连续治疗5天(n = 2)或7天(n = 2),而另外四匹矮种马作为未治疗的对照。治疗方案在接种前1小时开始。每天监测矮种马的临床症状。在接种后0、1、2、3、4、5、7、9、11、14、17和21天(dpi),采集鼻咽黏液样本以确定病毒排出情况。在相同时间点,采集血液并分离外周血单核细胞(PBMC)以确定病毒血症。在治疗期间,每天采集6次血样,即在服用伐昔洛韦前和1小时后,以确定血浆中阿昔洛韦的浓度。还采集鼻咽拭子以测量鼻分泌物中阿昔洛韦的浓度。在接受伐昔洛韦治疗和未治疗的矮种马之间未发现差异。两组的临床症状、病毒排出和病毒血症相似。在接受伐昔洛韦治疗的矮种马中,血浆阿昔洛韦浓度在整个治疗期的50%时间内可维持在EHV1的半数有效浓度(EC(50))以上。在鼻拭子中可检测到阿昔洛韦,其浓度为相应血浆浓度的50%至100%。尽管血浆和鼻黏液中可达到足够高的阿昔洛韦水平,但伐昔洛韦治疗对EHV1感染矮种马的临床症状、病毒排出和病毒血症没有影响。