Klecker R W, Collins J M, Yarchoan R, Thomas R, Jenkins J F, Broder S, Myers C E
Clin Pharmacol Ther. 1987 Apr;41(4):407-12. doi: 10.1038/clpt.1987.49.
We investigated the clinical pharmacokinetics of azidothymidine (N3TdR) as part of a phase I/II trial in the treatment of acquired immunodeficiency syndrome and related diseases. During the 6-week course of therapy, drug levels in plasma, cerebrospinal fluid, and urine were determined by HLPC. The plasma half-life of N3TdR was 1.1 hour. The total body clearance was 1.3 L/kg/hr. At intravenous doses of 5 mg/kg or oral doses of 10 mg/kg, plasma levels were continuously maintained above the target level of 1 mumol/L. Oral bioavailability was 63% +/- 13%. Substantial penetration of N3TdR into cerebrospinal fluid was demonstrated. At doses of 5 mg/kg intravenously or 10 mg/kg orally, cerebrospinal fluid drug levels exceeded and were maintained close to 1 mumol/L. Nineteen percent of the administered dose was excreted unchanged into the urine. Renal clearance was 0.23 L/kg/hr. N3TdR possesses pharmacokinetic properties that would facilitate the long-term treatment of patients with acquired immunodeficiency syndrome: it can be given orally and it penetrates the central nervous system.
作为治疗获得性免疫缺陷综合征及相关疾病的 I/II 期试验的一部分，我们研究了叠氮胸苷（N3TdR）的临床药代动力学。在为期 6 周的治疗过程中，通过高效液相色谱法（HLPC）测定血浆、脑脊液和尿液中的药物水平。N3TdR 的血浆半衰期为 1.1 小时。全身清除率为 1.3 L/kg/小时。静脉注射剂量为 5 mg/kg 或口服剂量为 10 mg/kg 时，血浆水平持续维持在目标水平 1 μmol/L 以上。口服生物利用度为 63%±13%。已证实 N3TdR 可大量渗透入脑脊液。静脉注射剂量为 5 mg/kg 或口服剂量为 10 mg/kg 时，脑脊液药物水平超过并维持在接近 1 μmol/L。给药剂量的 19%以原形排泄到尿液中。肾清除率为 0.23 L/kg/小时。N3TdR 具有有利于获得性免疫缺陷综合征患者长期治疗的药代动力学特性：它可以口服给药并且能穿透中枢神经系统。
