阿德福韦二吡呋酯在猕猴体内的药代动力学及在大鼠体内的组织分布

目的　研究了新型抗病毒药物阿德福韦二吡呋酯 (ADV)po给药后在动物体内的吸收、分布、代谢和消除过程。方法　采用液相色谱质谱联用方法测定样品中的药物浓度。结果　猕猴po或iv给药ADV后 ,血液中只检测到活性代谢物阿德福韦(ADF) ,因此用ADF的血药浓度 时间曲线来估算药代动力学参数。猕猴poADV后 ,tmax为 0 .99～ 1.70h ,t1/ 2 为 1.6 4～ 5 .4 3h ,Cl为 9.14～ 13.91L·h- 1·kg- 1,绝对生物利用度为 19.9%。连续 7dpo给药(每日 1次 )后未发现药物累积现象。肾脏和肝脏中ADF的含量仅次于胃肠内容物。ADF主要经肾脏排出体外。结论　在给药量范围内表现为线性动力学 ,在靶器官肝脏中分布较多 ,主要从尿液中排出。

Pharmacokinetics of adefovir dipivoxil in monkeys and its distribution in rat tissues

AIM To reveal the process of absorption, distribution, metabolism and elimination of the antivirus agent adefovir dipivoxil (A DV) by animal body. METHODS Analyzing the concentration of adefovir(ADF) with LC/MS/MS method. RESULTS ADV transformed into ADF completely in plasma after po and iv administration of ADV to monkeys, so pharmacokinetic parameters were evaluated with the concentration time curves of ADF. The pharmacokinetic courses of ADF was independent of doses. After single -dose po administration of ADV to monkeys, t_max ranged from 0.99 h to 1.70 h, t_1/2 from 1.64 h to 5.43 h, Cl from 9.14 L·h^-1·kg^-1 to 13.91 L·h^-1·kg^-1, absolute bioavailability was 19.9%. After multi-dose (7 d, once everyday) po administration of ADV to monkeys, no drug cumulation was observed. ADF concentrations in liver and kidney were higher than other tissues besides stomach and intestine. Most of the metabolite of ADV was excreted from urine. CONCLUSION In dosage range studied pharmacokinetic behavior appeared as linear kinetic. The concentration of ADF was higher than most other tissues in liver, the target organ. ADF was excreted out of body mainly from urine.