A SINGLE-DOSE STUDY TO ASSESS THE PENETRATION OF STAVUDINE INTO HUMANCEREBROSPINAL-FLUID IN ADULTS

Penetration of stavudine into the cerebrospinal fluid (CSF) was studie d in healthy humans. In this open, randomized study, a single oral dos e of 40 mg of stavudine was given to 12 fasting volunteers greater tha n or equal to 18 years of age. Subjects were divided into three groups based on the time of CSF sampling (i.e., 0.75-1.25, 2-3, or 4-5 hours after dosing). Blood samples were collected over an 8-hour period aft er dosing and included a sample simultaneous with CSF collection to pe rmit an estimate of CSF: plasma ratios. Stavudine concentrations in pl asma and CSF were determined by a validated high-performance liquid ch romatography method. Repeated measurements of vital signs, physical ex amination, and clinical laboratory tests indicated that the stavudine dose was well tolerated. CSF levels were not detected 0.75 to 1.25 hou rs after dosing. Thereafter, levels were detected in the CSF of five s ubjects; the mean concentration was 61 ng/ml. The mean CSF: plasma rat io increased with time, from 0.16 at 2 to 3 hours postdose in one subj ect to 0.40 at 4 to 5 hours postdose in four subjects. In conclusion, the mean stavudine concentration of 61 ng/ml achieved in the CSF of fi ve subjects exceeds the ED50 of clinical isolates of HIV (230 nM, 52 n g/ml).