Pharmacokinetics of isavuconazole in healthy cats after oral and intravenous administration.
Pharmacokinetics of isavuconazole in healthy cats after oral and intravenous administration.
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DOI：
10.1111/jvim.16452
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发表时间：
2022-07
影响因子：
2.6
通讯作者：
Dear, Jonathan D.
中科院分区：
文献类型：
--
作者：
Woerde, Dennis J.;Wittenburg, Luke A.;Dear, Jonathan D.
异武康唑是一种三氮唑类抗真菌药物，已在人类患者中显示出良好的疗效。猫的吸收和药代动力学尚未得到评估。目的：测定单次静脉注射或口服异武康唑的猫体内的药代动力学。八只健康的成年研究猫。4只猫接受100mg异武康唑PO胶囊治疗。4只猫静脉注射5 mg/kg异伍康唑溶液。每隔一段时间采集血清，用超高效液相色谱-串联质谱仪进行分析。数据分析采用两室均匀加权药代动力学分析，PO给药具有滞后时间，静脉给药采用两室、1/年加权。预测给药间隔为24小时和48小时，给药间隔为100 mg异武康唑，并评估了体外血浆蛋白结合。PO和IV给药均导致较高的血药浓度。静脉注射和PO制剂的异武康唑似乎能够互换使用。血药浓度峰值在给药后5 ± 3.8h，消除半衰期为66.2 ± 55.3h。PO组和IV组的受试者间变异性都很明显。两只猫在服用PO后6至8小时内呕吐。静脉注射组未见不良反应。口服生物利用度估计约为88%。血清蛋白结合率约为99.0% ± 0.03%。鉴于其良好的药代动力学，异武康唑可能被证明对患有真菌病的猫有用。还需要对长期使用异武康唑的安全性、有效性和耐受性进行进一步的研究。
Isavuconazole is a triazole antifungal drug that has shown good efficacy in human patients. Absorption and pharmacokinetics have not been evaluated in cats. To determine the pharmacokinetics of isavuconazole in cats given a single IV or PO dose. Eight healthy, adult research cats. Four cats received 100 mg capsules of isavuconazole PO. Four cats received 5 mg/kg isavuconazole solution IV. Serum was collected at predetermined intervals for analysis using ultra‐high performance liquid chromatography‐tandem mass spectrometry. Data were analyzed using a 2‐compartment uniform weighting pharmacokinetic analysis with lag time for PO administration and a 2 compartment, 1/y2 weighting for IV administration. Predicted 24 and 48‐hour dosing intervals of 100 mg isavuconazole administered PO were modeled and in vitro plasma protein binding was assessed. Both PO and IV drug administration resulted in high serum concentrations. Intravenous and PO formulations of isavuconazole appear to be able to be used interchangeably. Peak serum isavuconazole concentrations occurred 5 ± 3.8 hours after PO administration with an elimination rate half‐life of 66.2 ± 55.3 hours. Intersubject variability was apparent in both the PO and IV groups. Two cats vomited 6 to 8 hours after PO administration. No adverse effects were observed in the IV group. Oral bioavailability was estimated to be approximately 88%. Serum protein binding was calculated to be approximately 99.0% ± 0.03%. Isavuconazole might prove to be useful in cats with fungal disease given its favorable pharmacokinetics. Additional studies on safety, efficacy, and tolerability of long‐term isavuconazole use are needed.
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影响因子：
1.7
作者：
Papastefanou, Anastasia K.;Galatos, Apostolos D.;Kostoulas, Polychronis
通讯作者：
Kostoulas, Polychronis
影响因子：
4.9
作者：
Schmitt-Hoffmann, A;Roos, B;Beglinger, C
通讯作者：
Beglinger, C
DOI：
10.2147/dddt.s145545
发表时间：
2018
期刊：
Drug design, development and therapy
影响因子：
--
作者：
Jenks JD;Salzer HJ;Prattes J;Krause R;Buchheidt D;Hoenigl M
通讯作者：
Hoenigl M
影响因子：
5.2
作者：
Warn, PA;Sharp, A;Denning, DW
通讯作者：
Denning, DW
影响因子：
4.9
作者：
Kosmidis, Chris;Otu, Akan;Rautemaa-Richardson, Riina
通讯作者：
Rautemaa-Richardson, Riina