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Stavudine Entry into Cerebrospinal Fluid After Single and Multiple Doses in Patients Infected with Human Immunodeficiency Virus
Author(s) -
Brady Kathleen A.,
Boston Ray C.,
Aldrich Jennifer L.,
MacGregor Rob Roy
Publication year - 2005
Publication title -
pharmacotherapy: the journal of human pharmacology and drug therapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 109
eISSN - 1875-9114
pISSN - 0277-0008
DOI - 10.1592/phco.25.1.10.55625
Subject(s) - stavudine , dosing , medicine , cerebrospinal fluid , pharmacokinetics , gastroenterology , anesthesia , pharmacology , human immunodeficiency virus (hiv) , viral load , immunology , antiretroviral therapy
Study Objective. To establish the pharmacokinetics of stavudine within the cerebrospinal fluid (CSF) of patients infected with human immunodeficiency virus (HIV). Design. Pharmacokinetic study. Setting. General clinical research center. Patients. Thirty‐six patients infected with HIV; 21 were receiving long‐term stavudine therapy, 15 were not (single‐dose treatment group). Intervention. After an overnight fast, all patients received a single dose of stavudine 40 mg. Fifteen patients in the long‐term treatment group and all 15 patients in the single‐dose treatment group were randomized to undergo lumbar puncture 2, 4, or 6 hours after dosing (five patients for each time point from each group). The six other patients in the long‐term treatment group underwent lumbar puncture 0 or 8 hours after dosing. Measurements and Main Results. Serum stavudine concentrations were obtained just before dosing, 1 hour after dosing (approximate peak), and at the time of lumbar puncture. The CSF was also analyzed for cell counts, protein, and glucose levels. The mean peak serum stavudine concentration in the long‐term treatment group was estimated to be 580.7 ng/ml (2.59 μmol/L), occurring approximately 1.3 hours after dosing. The CSF concentrations over 0–8 hours were 0.0–109.9 ng/ml (0.00–0.49 μmol/L) with an overall mean of 51.6 ng/ml (0.23 μmol/L). Mean peak CSF concentration was estimated to be 62.8 ng/ml (0.28 μmol/L), occurring 4.7 hours after dosing. For the 15 patients not taking stavudine, both the serum and the CSF estimated peaks were significantly lower than those of the long‐term group: 475.3 ng/ml (2.12 μmol/L) and 40.4 ng/ml (0.18 μmol/L), respectively. However, time to peak was similar at 1.2 hours and 5.0 hours, respectively. In both groups, no correlation was found between CSF and baseline or peak serum stavudine concentrations, CSF white blood cell count, baseline CD4+ lymphocyte count, or plasma viral load. Conclusion. Mean CSF stavudine concentrations equaled or exceeded the mean concentration producing 50% of the maximal effect in vivo (EC 50 ) for HIV. The CSF concentrations were higher in the stavudine‐experienced patients, indicating that concentrations rise with progressive doses until steady state is reached.