Acyclovir concentrations in serum and cerebrospinal fluid at steady state

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Abstract
A long-term clinical trial of acyclovir, 800 mg tid, as a therapeutic agent in multiple sclerosis (MS) is in progress. In three patients paired serum and cerebrospinal fluid (CSF) specimens were sampled after one, four, eight and twelve months of continuous treatment These samples were collected 1·5 h before or 1·5 h after an oral dose. Acyclovir concentrations were assessed by radioimmunoassay. In the CSF, the acyclovir concentration was relatively stable, with a mean of 0-83 μM, while the serum acyclovir concentration was variable with mean peak and trough concentrations of 4·08 and 2·47 μM, respectively. In two other MS patients the acyclovir concentration time profile in serum and CSF was studied at steady state during the 8 h dose interval. In this study the acyclovir concentration in the CSF was only slightly affected by the fluctuations in serum and the acyclovir CSF/acyclovir serum ratio was apparently not influenced by the blood-brain barrier function. We found no indication of an accumulation of acyclovir in cerebrospinal fluid after one to twelve months of oral treatment.