Plasma and cerebrospinal fluid pharmacokinetics of 3'-azido-3'-deoxythymidine: a novel pyrimidine analog with potential application for the treatment of patients with AIDS and related diseases

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.

Publication types

  • Clinical Trial

MeSH terms

  • Acquired Immunodeficiency Syndrome / drug therapy
  • Acquired Immunodeficiency Syndrome / metabolism*
  • Administration, Oral
  • Biological Availability
  • Chromatography, High Pressure Liquid
  • Clinical Trials as Topic
  • Drug Evaluation
  • Half-Life
  • Humans
  • Infusions, Intravenous
  • Kinetics
  • Thymidine / analogs & derivatives*
  • Thymidine / blood
  • Thymidine / cerebrospinal fluid
  • Thymidine / metabolism
  • Thymidine / therapeutic use
  • Zidovudine


  • Zidovudine
  • Thymidine