Lee D-U, Je S H, Yoo S J, Kwon T, Shin J Y, Byun J J, Park J-H, Jeong K-W, Ku J-M, Lyoo Y S
Department of Immunopathology, College of Veterinary Medicine, Konkuk University, Seoul, South Korea.
Center for FMD Vaccine Research, Animal and Plant Quarantine Agency, Gimcheon-si, South Korea.
J Vet Pharmacol Ther. 2017 Oct;40(5):561-568. doi: 10.1111/jvp.12394. Epub 2017 Feb 15.
Ribavirin (RBV) is a synthetic guanosine analog that is used as a drug against various viral diseases in humans. The in vitro antiviral effects of ribavirin against porcine viruses were demonstrated in several studies. The purposes of this study were to evaluate the adverse effects and pharmacokinetics of ribavirin following its intramuscular (IM) injection in pigs. Ribavirin was formulated as a double-oil emulsion (RBV-DOE) and gel (RBV-Gel), which were injected into the pigs as single-dose IM injections. After injection of RBV, all of the pigs were monitored. The collected serum and whole blood samples were analyzed by liquid chromatography-tandem mass spectrometry and complete blood count analysis, respectively. All of the ribavirin-treated pigs showed significant decreases in body weight compared to the control groups. Severe clinical signs including dyspnea, anorexia, weakness, and depression were present in ribavirin-treated pigs until 5 days postinjection (dpi). The ribavirin-treated groups showed significant decrease in the number of red blood cells and hemoglobin concentration until 8 dpi. The mean half-life of the RBV-DOE and RBV-Gel was 27.949 ± 2.783 h and 37.374 ± 3.502 h, respectively. The mean peak serum concentration (C ) and area under the serum concentration-time curve from time zero to infinity (AUC ) of RBV-DOE were 8340.000 ± 2562.577 ng/mL and 16 0095.430 ± 61 253.400 h·ng/mL, respectively. The C and AUC of RBV-Gel were 15 300.000 ± 3764.306 ng/mL and 207526.260 ± 63656.390 h·ng/mL, respectively. The results of this study provided the index of side effect and pharmacokinetics of ribavirin in pigs, which should be considered before clinical application.
利巴韦林（RBV）是一种合成鸟苷类似物，用作治疗人类各种病毒性疾病的药物。多项研究证实了利巴韦林对猪病毒的体外抗病毒作用。本研究的目的是评估利巴韦林肌肉注射（IM）给猪后产生的不良反应和药代动力学。利巴韦林被制成双油乳剂（RBV-DOE）和凝胶剂（RBV-Gel），以单剂量肌肉注射的方式注入猪体内。注射RBV后，对所有猪进行监测。分别通过液相色谱-串联质谱法和全血细胞计数分析对采集的血清和全血样本进行分析。与对照组相比，所有接受利巴韦林治疗的猪体重均显著下降。直到注射后5天（dpi），接受利巴韦林治疗的猪出现了包括呼吸困难、厌食、虚弱和抑郁在内的严重临床症状。直到8 dpi，接受利巴韦林治疗的组红细胞数量和血红蛋白浓度显著下降。RBV-DOE和RBV-Gel的平均半衰期分别为27.949±2.783小时和37.374±3.502小时。RBV-DOE的平均血清峰值浓度（C）和从零到无穷大的血清浓度-时间曲线下面积（AUC）分别为8340.000±2562.577 ng/mL和160095.430±61253.400 h·ng/mL。RBV-Gel的C和AUC分别为15300.000±3764.306 ng/mL和207526.260±63656.390 h·ng/mL。本研究结果提供了利巴韦林在猪体内的副作用指标和药代动力学，临床应用前应予以考虑。
