Garré B, Baert K, Nauwynck H, Deprez P, De Backer P, Croubels S
Department of Pharmacology, Toxicology and Biochemistry, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
J Vet Pharmacol Ther. 2009 Jun;32(3):207-12. doi: 10.1111/j.1365-2885.2008.01025.x.
The aim of the current study was to investigate whether multiple oral dosing of valacyclovir could result in plasma concentrations exceeding the EC(50)-value of acyclovir against equine herpesvirus 1 (EHV1) during the majority of the treatment period. Additionally, we wanted to determine the concentration of acyclovir in nasal mucus and cerebrospinal fluid (CSF). Valacyclovir was administered to four horses and two ponies, three times daily, at a dosage of 40 mg/kg, for four consecutive days. Blood was collected prior to each administration and 1 h after dosing. Nasal mucus samples and CSF were collected once during treatment; 1 h after the last administration. This dosage regimen resulted in plasma concentrations that were higher than the EC(50)-value of 1.7 microg/mL, i.e. EC(50) of an isolate highly susceptible to acyclovir, for 80% of the treatment period; and higher than the EC(50)-value of 3.0 microg/mL, i.e. EC(50) of an isolate less susceptible to acyclovir, for 60% of the treatment period. Concentration in nasal mucus samples and CSF was 0.36-1.17 microg/mL and 0.11-0.23 microg/mL, respectively. This study illustrates that multiple dosing of valacyclovir may result in a therapeutic benefit as plasma concentrations could be maintained above the EC(50)-value of acyclovir against EHV1 for more than 50% of the treatment period. Acyclovir could be detected in both nasal mucus samples and CSF. However, these concentrations were lower than the EC(50).
本研究的目的是调查多次口服伐昔洛韦是否会导致在大部分治疗期间血浆浓度超过阿昔洛韦对马疱疹病毒1型（EHV1）的半数有效浓度（EC50）。此外，我们还想确定阿昔洛韦在鼻黏液和脑脊液（CSF）中的浓度。对4匹马和2匹小马每日3次给予伐昔洛韦，剂量为40mg/kg，连续给药4天。在每次给药前和给药后1小时采集血液。在治疗期间采集一次鼻黏液样本和脑脊液；在最后一次给药后1小时采集。这种给药方案导致血浆浓度在80%的治疗期间高于1.7μg/mL的EC50值，即对阿昔洛韦高度敏感的分离株的EC50；在60%的治疗期间高于3.0μg/mL的EC50值，即对阿昔洛韦敏感性较低的分离株的EC50。鼻黏液样本和脑脊液中的浓度分别为0.36 - 1.17μg/mL和0.11 - 0.23μg/mL。本研究表明，多次服用伐昔洛韦可能会带来治疗益处，因为在超过50%的治疗期间血浆浓度可维持在阿昔洛韦对EHV1的EC50值以上。在鼻黏液样本和脑脊液中均能检测到阿昔洛韦。然而，这些浓度低于EC50。
