Feinberg A, Leyland-Jones B, Fanucchi M P, Hancock C, Fox J J, Watanabe K A, Vidal P M, Williams L, Young C W, Philips F S
Antimicrob Agents Chemother. 1985 May;27(5):733-8. doi: 10.1128/AAC.27.5.733.
The metabolism of the drug [2-14C]-1-(2'-deoxy-2'-fluoro-beta-D -arabinofuranosyl)-5-iodocytosine (FIAC), a potent inhibitor of herpesvirus replication, was studied in immunosuppressed patients with herpesvirus infections. FIAC was administered intravenously by 15-min infusion and by mouth 24 h later to four patients at doses of 50 or 100 mg/m2. FIAC was cleared from the plasma primarily by biotransformation in liver, kidney, and peripheral blood, with a terminal-phase half-life of 0.92 to 1.80 h (mean, 1.36 h) after intravenous administration. The area under the concentration-time curve from zero to infinity (AUC0-infinity) for FIAC was 1.6 to 4.7% (mean, 3.4%) of the AUC0-infinity for total radioactivity. 1-(2'-Deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodouracil (FIAU) was the major metabolite; the AUC0-infinity for FIAU was 54.3 to 72.5% (mean, 63.4%) of the AUC0-infinity for total radioactivity. The terminal-phase half-life for FIAU was 3.32 to 4.49 h (mean, 3.91 h); FIAU was cleared from plasma by renal elimination and further biotransformation. lesser amounts of 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)uracil, 1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)cytosine, the glucuronide conjugates of these metabolites, and the glucuronide conjugates of FIAC and FIAU were also formed. A comparison of the AUC0-infinity for total radioactivity after intravenous and oral administration suggested that nearly all of the oral dose was absorbed. Plasma levels of FIAU, also a potent inhibitor of herpesvirus replication in vitro, exceeded the 50% effective dose for herpes simplex virus and varicella-zoster virus as late as 12 h after administration of FIAC.
对强效疱疹病毒复制抑制剂[2-14C]-1-(2'-脱氧-2'-氟-β-D-阿拉伯呋喃糖基)-5-碘胞嘧啶（FIAC）在患有疱疹病毒感染的免疫抑制患者体内的代谢情况进行了研究。对4名患者以50或100mg/m2的剂量静脉输注15分钟给予FIAC，并在24小时后口服给药。FIAC主要通过肝脏、肾脏和外周血中的生物转化从血浆中清除，静脉给药后终末相半衰期为0.92至1.80小时（平均1.36小时）。FIAC从零至无穷大的浓度-时间曲线下面积（AUC0-∞）占总放射性AUC0-∞的1.6%至4.7%（平均3.4%）。1-(2'-脱氧-2'-氟-β-D-阿拉伯呋喃糖基)-5-碘尿嘧啶（FIAU）是主要代谢产物；FIAU的AUC0-∞占总放射性AUC0-∞的54.3%至72.5%（平均63.4%）。FIAU的终末相半衰期为3.32至4.49小时（平均3.91小时）；FIAU通过肾脏排泄和进一步生物转化从血浆中清除。还形成了少量的1-(2'-脱氧-2'-氟-β-D-阿拉伯呋喃糖基)尿嘧啶、1-(2'-脱氧-2'-氟-β-D-阿拉伯呋喃糖基)胞嘧啶、这些代谢产物的葡萄糖醛酸结合物以及FIAC和FIAU的葡萄糖醛酸结合物。静脉给药和口服给药后总放射性AUC0-∞的比较表明，几乎所有口服剂量都被吸收。FIAU在体外也是一种强效疱疹病毒复制抑制剂，在给予FIAC后12小时，其血浆水平仍超过单纯疱疹病毒和水痘-带状疱疹病毒的50%有效剂量。
