Rand K H, Raad I, el Koussi A, Houck H J, Brey W, Rocca J, Loftsson T, Bodor N
Department of Pathology, Gainesville Veterans Administration Medical Center, Florida.
J Virol Methods. 1987 Dec;18(4):257-69. doi: 10.1016/0166-0934(87)90087-5.
Trifluorothymidine (TFT) is known to be concentrated in herpes simplex virus (HSV) infected cells in vitro in the form of phosphorylated derivatives. We studied a murine hepatitis model of HSV infection to determine whether this in vitro observation would also be demonstrable in vivo. Following i.v. injection of 100 or 160 mg/kg TFT, TFT was found in significantly higher concentrations in the livers of HSV-2 infected mice than in the livers of uninfected mice, mice infected with murine hepatitis virus (MHV-A59) or mice with hepatitis from carbon tetrachloride treatment. Neither altered renal function, nor altered pharmacokinetics could account for this difference. 19F Nuclear Magnetic Resonance spectroscopy readily detected the 19F from TFT in both liver extracts and whole livers, particularly at higher tissue levels, i.e. greater than 50 micrograms/g tissue. If further studies with living animals support these preliminary observations, clinical application could be pursued.
三氟胸苷(TFT)已知在体外以磷酸化衍生物的形式集中于单纯疱疹病毒(HSV)感染的细胞中。我们研究了HSV感染的小鼠肝炎模型,以确定这种体外观察结果在体内是否也能得到证实。静脉注射100或160mg/kg的TFT后,发现HSV - 2感染小鼠肝脏中TFT的浓度显著高于未感染小鼠、感染鼠肝炎病毒(MHV - A59)的小鼠或接受四氯化碳治疗的肝炎小鼠的肝脏。肾功能改变或药代动力学改变均不能解释这种差异。19F核磁共振光谱很容易在肝脏提取物和整个肝脏中检测到来自TFT的19F,特别是在较高的组织水平,即大于50微克/克组织时。如果对活体动物的进一步研究支持这些初步观察结果,就可以进行临床应用。