Court Michael H, Robbins Alison H, Whitford Anne M, Beck Erika V, Tseng Flo S, Reeder DeeAnn M
Am J Vet Res. 2017 Jan;78(1):90-99. doi: 10.2460/ajvr.78.1.90.
OBJECTIVE To determine the pharmacokinetics of terbinafine in little brown myotis (Myotis lucifugus) infected with Pseudogymnoascus destructans. ANIMALS 123 bats from a P destructans-infected hibernation site in Virginia. PROCEDURES 3 bats were euthanized and necropsied to confirm the presence of P destructans within the population. The remaining 120 bats were systematically assigned to 6 groups (20 bats/group). Bats in each of 3 groups received 6, 20, or 60 mg of terbinafine/kg, SC, once daily for 10 days. Bats in another group received 200 mg of terbinafine/kg, SC, once daily for 5 days. Bats in 1 group received the terbinafine vehicle solution (0.1 mL/kg, SC, once daily for 10 days). Bats in the remaining group did not receive any treatment. Following the treatment period (days 1 through 10), bats were housed in a hibernation chamber and monitored daily until euthanasia on day 42, 75, or 109. Tissue specimens were collected from all bats as soon as possible after death or euthanasia to determine terbinafine concentration. Within each group and tissue type, terbinafine concentration data were pooled, and pharmacokinetic parameters were calculated by noncompartmental methods. RESULTS Adverse neurologic effects and a high mortality rate before day 10 were observed in bats that received the highest terbinafine dose (200 mg/kg) but not those that received lower doses. Presumed therapeutic terbinafine concentrations (≥ 2 μg/g) were maintained in skin and wing for at least 30 and 6 days in bats that received the 60 and 20 mg/kg doses, respectively, but were not achieved in most bats that received the 6 mg/kg dose. Tissue terminal half-life ranged from 14 to 22 days. Terbinafine concentration in hair was positively correlated with that in skin and wing. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated terbinafine doses > 6 but < 200 mg/kg should be further evaluated for the treatment of P destructans-infected bats. Collection of serial hair specimens may represent a noninvasive method for monitoring terbinafine concentration in treated bats.
目的 确定特比萘芬在感染了白腐假裸囊菌的小鼠耳蝠（Myotis lucifugus）体内的药代动力学。动物 从弗吉尼亚州一个感染白腐假裸囊菌的冬眠地点采集的123只蝙蝠。方法 对3只蝙蝠实施安乐死并进行尸检，以确认种群中存在白腐假裸囊菌。其余120只蝙蝠被系统地分为6组（每组20只）。3组中的每组蝙蝠分别接受6、20或60mg/kg的特比萘芬，皮下注射，每日1次，共10天。另一组蝙蝠接受200mg/kg的特比萘芬，皮下注射，每日1次，共5天。一组蝙蝠接受特比萘芬溶媒溶液（0.1mL/kg，皮下注射，每日1次，共10天）。其余组的蝙蝠不接受任何治疗。在治疗期（第1天至第10天）后，将蝙蝠安置在冬眠室中，每日进行监测，直至在第42、75或109天实施安乐死。在蝙蝠死亡或安乐死后尽快采集所有蝙蝠的组织标本，以测定特比萘芬浓度。在每组和每种组织类型中，汇总特比萘芬浓度数据，并通过非房室方法计算药代动力学参数。结果 在接受最高特比萘芬剂量（200mg/kg）的蝙蝠中观察到第10天前出现不良神经效应和高死亡率，但接受较低剂量的蝙蝠未出现。接受60和20mg/kg剂量的蝙蝠，其皮肤和翅膀中的特比萘芬假定治疗浓度（≥2μg/g）分别维持至少30天和6天，但接受6mg/kg剂量的大多数蝙蝠未达到该浓度。组织终末半衰期为14至22天。毛发中的特比萘芬浓度与皮肤和翅膀中的浓度呈正相关。结论及临床意义 结果表明，对于治疗感染白腐假裸囊菌的蝙蝠，应进一步评估剂量大于6但小于200mg/kg的特比萘芬。采集连续的毛发标本可能是监测经治疗蝙蝠体内特比萘芬浓度的一种非侵入性方法。
