Pharmacokinetic variability of zidovudine in HIV-infected individuals: subgroup analysis and drug interactions

AIDS. 1994 Dec;8(12):1683-9. doi: 10.1097/00002030-199412000-00007.


Objective: To investigate determinants of inter- and intraindividual variability of zidovudine (ZDV) pharmacokinetics in HIV-infected patients.

Design: A prospective study in a general 525-bed hospital with special funding for treatment and research of HIV-infected patients.

Methods: Serial blood samples were collected from 68 HIV-infected individuals providing a total of 95 pharmacokinetic curves. ZDV was measured with high-performance liquid chromatography and radioimmunoassay. Pharmacokinetic parameters were calculated by non-compartmental analysis. Patient characteristics were investigated by multivariate analysis for an influence on ZDV pharmacokinetics.

Results: Apparent ZDV clearance was significantly lower in patients with a lower body weight, in women, and in patients with a more advanced stage of HIV disease. Co-administration of methadone with ZDV resulted in higher plasma concentrations of ZDV, while rifampin and ganciclovir increased apparent ZDV clearance. Age, the duration of ZDV use, CD4+ cell count, creatinine clearance, elevated serum liver enzyme levels, and the use of 11 other co-administered medications were not independently related to apparent ZDV clearance.

Conclusions: The pharmacokinetic profile of ZDV in several subpopulations has been evaluated, as well as the observation of possible drug-drug interactions between ZDV and 14 different drugs or groups of drugs. These data suggest that patient-individualized antiretroviral therapy may be appropriate once pharmacokinetic-pharmacodynamic relationships have been established.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Body Weight
  • Drug Interactions
  • Female
  • HIV Infections / blood
  • HIV Infections / drug therapy
  • HIV Infections / metabolism*
  • HIV-1*
  • Humans
  • Kidney / physiopathology
  • Liver / physiopathology
  • Male
  • Middle Aged
  • Prospective Studies
  • Sex Characteristics
  • Zidovudine / administration & dosage
  • Zidovudine / blood
  • Zidovudine / pharmacokinetics*


  • Zidovudine