PDF(Pubmed)
Abstract：
UNASSIGNED: Fungal diseases are frequently associated with elevated mortality rates in elasmobranchs. Currently, there is a notable absence of scientifically validated therapeutic medications that can ensure both effectiveness and safety when administered to this group of animals. The empirical prescription of azole antifungal agents, particularly voriconazole, has been posited as a potentially efficacious treatment approach for addressing most common mycoses in sharks and rays. However, there are still no published pharmacokinetic studies supporting its use in elasmobranchs and there is a lack of scientific base for its utilization in elasmobranchs.
UNASSIGNED: For this study, voriconazole was administered intravenously (IV) and intramuscularly (IM), at a single dose of 4 mg/kg to six adult undulate skates (Raja undulata). A washout period of 8 weeks was left between each route of administration. Blood samples were collected both before and at ten predetermined intervals after each dosing (0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, and 36 h after drug administration). Plasma concentrations were quantified using a validated high-performance liquid chromatography method, and pharmacokinetic (PK) data was analyzed through non-compartmental methods.
UNASSIGNED: The mean extrapolated concentration at 0 h (C0) after IV administration was 27.19 ± 7.15 μg/mL and the mean peak plasma concentrations (Cmax) ± SEM after IM administration resulted 2.98 ± 0.28 μg/mL at a mean time to maximum concentration (T max) of 1.33 ± 0.17 h. Terminal half-lives were calculated and resulted 11.18 ± 1.32 h for IV injections and 9.59 ± 1.38 h for IM injections. The area under the curve extrapolated to infinity was determined as 58.14 ± 2.79 h·μg/ml following IV injections and 37.60 ± 6.67 h·μg/ml following IM injections. The IM-administered voriconazole exhibited a mean absolute bioavailability of 64.67 ± 11.47%.
UNASSIGNED: These discoveries provide backing for the possible application of voriconazole through the intramuscular route in undulate skates and support using lower dosage regimens compared to those required for oral administration, emphasizing the importance of conducting further pharmacokinetic studies with antifungals in elasmobranchs.
UNASSIGNED: For this study, voriconazole was administered intravenously (IV) and intramuscularly (IM), at a single dose of 4 mg/kg to six adult undulate skates (Raja undulata). A washout period of 8 weeks was left between each route of administration. Blood samples were collected both before and at ten predetermined intervals after each dosing (0.25, 0.5, 1, 1.5, 2, 4, 8, 12, 24, and 36 h after drug administration). Plasma concentrations were quantified using a validated high-performance liquid chromatography method, and pharmacokinetic (PK) data was analyzed through non-compartmental methods.
UNASSIGNED: The mean extrapolated concentration at 0 h (C0) after IV administration was 27.19 ± 7.15 μg/mL and the mean peak plasma concentrations (Cmax) ± SEM after IM administration resulted 2.98 ± 0.28 μg/mL at a mean time to maximum concentration (T max) of 1.33 ± 0.17 h. Terminal half-lives were calculated and resulted 11.18 ± 1.32 h for IV injections and 9.59 ± 1.38 h for IM injections. The area under the curve extrapolated to infinity was determined as 58.14 ± 2.79 h·μg/ml following IV injections and 37.60 ± 6.67 h·μg/ml following IM injections. The IM-administered voriconazole exhibited a mean absolute bioavailability of 64.67 ± 11.47%.
UNASSIGNED: These discoveries provide backing for the possible application of voriconazole through the intramuscular route in undulate skates and support using lower dosage regimens compared to those required for oral administration, emphasizing the importance of conducting further pharmacokinetic studies with antifungals in elasmobranchs.
摘要：
■真菌疾病通常与弹性肌的死亡率升高有关。目前,明显缺乏经过科学验证的治疗药物,这些药物在对该组动物给药时可确保有效性和安全性.唑类抗真菌药的经验处方，尤其是伏立康唑,已被认为是解决鲨鱼和射线中最常见的真菌病的潜在有效治疗方法。然而,目前还没有发表的药代动力学研究支持其在弹枝中的使用，也缺乏其在弹枝中的使用的科学依据。
■对于这项研究，伏立康唑静脉内（IV）和肌内（IM）给药，以4mg/kg的单剂量给六个成年起伏的溜冰鞋（Rajaundulata）。在每种给药途径之间留下8周的清除期。在每次给药之前和之后以10个预定间隔(给药后0.25、0.5、1、1.5、2、4、8、12、24和36小时)收集血样。使用经过验证的高效液相色谱法对血浆浓度进行定量，和药代动力学（PK）数据通过非房室方法进行分析。
■IV给药后0h的平均外推浓度（C0）为27.19±7.15μg/mL，IM给药后的平均峰值血浆浓度（Cmax）±SEM在达到最大浓度的平均时间（Tmax）为1.33±0.17h时得出2.98±0.28μg/mL。IV注射后，外推到无穷大的曲线下面积确定为58.14±2.79h·μg/ml，IM注射后为37.60±6.67h·μg/ml。IM给药的伏立康唑表现出64.67±11.47%的平均绝对生物利用度。
■这些发现为伏立康唑在波浪形溜冰鞋中通过肌内途径的可能应用提供了支持，并且与口服给药所需的剂量相比，使用较低剂量的方案提供了支持，强调在弹性膜中使用抗真菌药进行进一步药代动力学研究的重要性。
■对于这项研究，伏立康唑静脉内（IV）和肌内（IM）给药，以4mg/kg的单剂量给六个成年起伏的溜冰鞋（Rajaundulata）。在每种给药途径之间留下8周的清除期。在每次给药之前和之后以10个预定间隔(给药后0.25、0.5、1、1.5、2、4、8、12、24和36小时)收集血样。使用经过验证的高效液相色谱法对血浆浓度进行定量，和药代动力学（PK）数据通过非房室方法进行分析。
■IV给药后0h的平均外推浓度（C0）为27.19±7.15μg/mL，IM给药后的平均峰值血浆浓度（Cmax）±SEM在达到最大浓度的平均时间（Tmax）为1.33±0.17h时得出2.98±0.28μg/mL。IV注射后，外推到无穷大的曲线下面积确定为58.14±2.79h·μg/ml，IM注射后为37.60±6.67h·μg/ml。IM给药的伏立康唑表现出64.67±11.47%的平均绝对生物利用度。
■这些发现为伏立康唑在波浪形溜冰鞋中通过肌内途径的可能应用提供了支持，并且与口服给药所需的剂量相比，使用较低剂量的方案提供了支持，强调在弹性膜中使用抗真菌药进行进一步药代动力学研究的重要性。
