Penetration of zidovudine into the cerebrospinal fluid of patients infected with HIV.

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.