Objective: To investigate penetration of zidovudine (ZDV) into the cerebrospinal fluid (CSF) of HIV-infected patients for whom a lumbar puncture was indicated.
Design: A prospective study.
Setting: General 525-bed hospital with special funding for treatment and research of HIV-infected patients.
Patients, participants: Thirty-nine patients with a medical indication for lumbar puncture who used ZDV chronically were included in this study (50 samples in total).
Main outcome measure: Determination of ZDV and proteins in CSF and plasma samples.
Results: CSF concentrations of ZDV showed little fluctuation 1-8 h after the last ingestion of ZDV. In contrast, plasma levels displayed large variability in this period and decreased exponentially over time. As a result, the CSF/plasma ratio increased linearly over time. No significant relation between the ZDV dose, neither the medical indication for lumbar puncture nor the protein ratio (as a measure for the integrity of the blood-brain barrier), and CSF levels of ZDV was found. The CSF/plasma ratio of ZDV did not give essential information on drug distribution into CSF.
Conclusions: Penetration of ZDV into the CSF appears to be independent of the dose (range, 200-1250 mg daily), which may be an explanation for the efficacy of low doses of ZDV in the prevention and treatment of HIV-related neurological diseases. ZDV levels were at steady-state during the first 6 h after ingestion. The CSF/plasma ratio of ZDV concentrations is not an appropriate marker for drug penetration into CSF.