PENETRATION OF 3'-AMINO-3'-DEOXYTHYMIDINE, A CYTOTOXIC METABOLITE OF ZIDOVUDINE, INTO THE CEREBROSPINAL-FLUID OF HIV-1-INFECTED PATIENTS

The penetration of 3'-amino-3'-deoxythymidine (AMT) into the cerebrosp inal fluid (CSF) of HIV-1-infected patients has been investigated. In 23 patients who used zidovudine (ZDV) chronically, CSF and plasma samp les were assayed for AMT and ZDV. The influences of time between ZDV o ral administration and lumbar puncture, of ZDV dose, and of the medica l indication for lumbar puncture based on the concentration of AMT in CSF and on the CSF-plasma concentration ratio were investigated. AMT c an be detected in the CSF after oral administration of ZDV; concentrat ions of AMT in CSF ranged from 0.75 to 4.8 ng/ml (median, 1.7 ng/ml). The median CSF-plasma concentration ratio was 1, and equaled that for ZDV. CSF and plasma concentrations of AMT were approximately threefold higher in patients with cerebral toxoplasmosis; the CSF-plasma concen tration ratio remained equal to unity in these cases. This phenomenon might be caused by a pharmacokinetic interaction between AMT and pyrim ethamine, sulfadiazine, folinic acid, or a combination of these. The c linical relevance of AMT, especially the possibility of decreased effi cacy of ZDV, throughout the body and in the central nervous system, an d the involvement of this metabolite in ZDV-induced myelosuppression, remains to be established.