二磷酸阿昔洛韦二肉豆蔻酰甘油在人巨细胞病毒感染细胞中的抗病毒作用、药代动力学及兔玻璃体内毒理学研究
Antiviral effect in human cytomegalovirus-infected cells, pharmacokinetics, and intravitreal toxicology in rabbits of acyclovir diphosphate dimyristoylglycerol.
作者信息
Shakiba S, Freeman W R, Flores-Aguilar M, Munguia D, Tatebayashi M, Besen G, Amani R, Wiley C A, Vuong C, Aldern K A
机构信息
Department of Ophthalmology, University of California, San Diego, La Jolla 92093, USA.
出版信息
Antimicrob Agents Chemother. 1995 Jun;39(6):1383-5. doi: 10.1128/AAC.39.6.1383.
Acyclovir diphosphate dimyristoylglycerol (ACVDP-DG) is a lipid prodrug which is active against ACV-resistant strains of herpes simplex virus because of its intracellular metabolism to ACV monophosphate. In human cytomegalovirus (HCMV)-infected MRC-5 cells, ACVDP-DG was ninefold more active than ACV. When liposomal [8-3H]ACVDP-DG was injected intravitreally at the maximum nontoxic dose of 1 mumol in rabbits, the drug remained above its estimated 90% HCMV-inhibitory concentration for 18 days. Intravitreal ganciclovir persists above its 90% inhibitory concentration for only 1 to 2 days. ACVDP-DG may be useful as a local treatment for HCMV retinitis.
阿昔洛韦二磷酸二肉豆蔻酰甘油（ACVDP-DG）是一种脂质前药，由于其在细胞内代谢为阿昔洛韦单磷酸，因此对单纯疱疹病毒的阿昔洛韦耐药菌株具有活性。在人巨细胞病毒（HCMV）感染的MRC-5细胞中，ACVDP-DG的活性比阿昔洛韦高9倍。当以1 μmol的最大无毒剂量将脂质体[8-3H]ACVDP-DG玻璃体内注射到兔子体内时，该药物在18天内一直保持在其估计的90% HCMV抑制浓度以上。玻璃体内注射更昔洛韦仅在1至2天内保持在其90%抑制浓度以上。ACVDP-DG可能作为HCMV视网膜炎的局部治疗药物有用。
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