Greig N H, Fredericks W R, Holloway H W, Soncrant T T, Rapoport S I
Laboratory of Neurosciences, National Institute on Aging, Bethesda, Maryland.
J Pharmacol Exp Ther. 1988 May;245(2):581-6.
Pharmacokinetic parameters of human lymphoblastoid interferon (IFN-alpha) delivery to normal rat brain were examined. IFN-alpha concentrations in brain parenchyma could only be detected 120 min after its intravascular administration, and were 0.003% per gram of the administered dose. The mean cerebrovascular permeability-surface area (permeability x surface area) product to IFN, 120 min after infusion, was 0.35 x 10(-6) sec-1, which is not significantly different from zero. Neither i.v. nor intracarotid IFN-alpha administration significantly affected delivery to brain. Intrathecal administration of IFN-alpha, via the cisterna magna, resulted in undetectable concentrations in brain tissue and plasma at 30 and 60 min. However, osmotic blood-brain barrier opening significantly increased IFN-alpha delivery to brain after its carotid administration. A maximum concentration of 0.18% per gram of the total administered dose was achieved at 120 min, and the cerebrovascular permeability-surface area was increased to 30.8 x 10(-6) sec-1. Intracerebral IFN-alpha concentrations did not decline significantly during the 240 min study. Osmotic blood-brain barrier opening increased the area under the brain concentration vs. time curve, measured between 30 and 240 min, from 0.012 x 10(6) U.min/g, in controls, to 1.24 x 10(6) U.min/g, at least 100-fold. This study indicates that osmotic blood-brain barrier opening significantly increases the delivery of IFN-alpha into brain, and that delivered remains within the brain for many hours.
研究了人淋巴母细胞干扰素（IFN-α）向正常大鼠脑内递送的药代动力学参数。血管内给药120分钟后，仅在脑实质中检测到IFN-α浓度，每克给药剂量中为0.003%。输注120分钟后，脑血管通透性-表面积（通透性×表面积）乘积对IFN而言为0.35×10⁻⁶秒⁻¹，与零无显著差异。静脉注射或颈动脉注射IFN-α均未显著影响其向脑内的递送。通过枕大池鞘内注射IFN-α，在30分钟和60分钟时脑组织和血浆中浓度均检测不到。然而，渗透性血脑屏障开放显著增加了颈动脉给药后IFN-α向脑内的递送。在120分钟时，每克总给药剂量达到最大浓度0.18%，脑血管通透性-表面积增加到30.8×10⁻⁶秒⁻¹。在240分钟的研究期间，脑内IFN-α浓度未显著下降。渗透性血脑屏障开放使30至240分钟期间测量的脑浓度-时间曲线下面积从对照组的0.012×10⁶单位·分钟/克增加到1.24×10⁶单位·分钟/克，至少增加了100倍。本研究表明，渗透性血脑屏障开放显著增加了IFN-α向脑内的递送，且递送的IFN-α在脑内可保持数小时。
