Meldrum J B, Gupta V S, Taneja A K, Sisodia C S
J Pharmacol Exp Ther. 1981 Feb;216(2):275-80.
Pharmacokinetic and pharmacodynamic properties of 5-methoxymethyl-2'-deoxyuridine (MMUdR), a drug with potent antiviral activity against herpes simplex virus, were investigated. After i.v. administration of [2-14C]MMUdR at 50 and 25 mg/kg to rats, the overall half life of the drug (T 1/2 Kel) was calculated to be 32 to 35 min. The biological half life of the drug (T 1/2 beta) was 89 min and the distribution half life (T1/2 alpha) was 6 min. The specific volume of distribution was calculated to be 1.28 to 1.35 liters/kg and the total body clearance rate of the drug was 10 ml/min/kg. The data were analyzed on the basis of a two-compartment open pharmacokinetic model. After i.p. administration of 50 mg/kg of [2-14C]MMUdR to mice, peak plasma levels of 35.6 micrograms/ml were attained in 10 min. The highest tissue concentrations of [2-14C]MMUdR in mice were 63 micrograms/g in kidneys (30 min) followed by 36 micrograms/g in liver and spleen and 30 to 32 micrograms/g in lungs and gut (20 min). MMUdR did not undergo biotransformation in plasma but urine was found to contain MMUdR (greater than 80%) and a small amount of radioactivity which comigrated with MMUdR monophosphate. Administration of 500 mg/kg of MMUdR i.v. to New Zealand White rabbits did not produce any observable effects on the heart rate, ECG pattern or respiration rate. Vasodilation of 39-sec duration was observed immediately after administration of MMUdR.
对具有抗单纯疱疹病毒强效抗病毒活性的药物5-甲氧基甲基-2'-脱氧尿苷（MMUdR）的药代动力学和药效学特性进行了研究。以50和25mg/kg的剂量给大鼠静脉注射[2-¹⁴C]MMUdR后，计算出该药物的总半衰期（T₁/₂ Kel）为32至35分钟。该药物的生物半衰期（T₁/₂β）为89分钟，分布半衰期（T₁/₂α）为6分钟。计算出的分布比容为1.28至1.35升/千克，该药物的总体清除率为10毫升/分钟/千克。根据二室开放药代动力学模型对数据进行了分析。以50mg/kg的剂量给小鼠腹腔注射[2-¹⁴C]MMUdR后，10分钟内血浆峰值水平达到35.6微克/毫升。小鼠中[2-¹⁴C]MMUdR的最高组织浓度在肾脏中为63微克/克（30分钟），其次是肝脏和脾脏中为36微克/克，肺和肠道中为30至32微克/克（20分钟）。MMUdR在血浆中未发生生物转化，但发现尿液中含有MMUdR（大于80%）和少量与MMUdR单磷酸共迁移的放射性物质。以500mg/kg的剂量给新西兰白兔静脉注射MMUdR对心率、心电图模式或呼吸频率未产生任何可观察到的影响。注射MMUdR后立即观察到持续39秒的血管舒张。
