The aciclovir metabolite CMMG is detectable in the CSF of subjects with neuropsychiatric symptoms during aciclovir and valaciclovir treatment.

Abstract

OBJECTIVES:

Neuropsychiatric symptoms related to aciclovir or valaciclovir treatment have been a problem since aciclovir was introduced in the early 1980s. We have previously found that subjects with aciclovir-related neuropsychiatric symptoms have increased serum concentrations of aciclovir's main metabolite, 9-carboxymethoxymethylguanine (CMMG). The aim of this study was to investigate whether CMMG was present in the CSF of aciclovir- or valaciclovir-treated subjects with or without neuropsychiatric side effects that appeared during therapy.

METHODS:

We investigated retrospectively CSF collected from 21 aciclovir- or valaciclovir-treated subjects. Of these, 9 were subjects with neuropsychiatric signs and symptoms and 12 were asymptomatic subjects, including 10 subjects from a valaciclovir multiple sclerosis trial and 2 subjects with recurrent herpes encephalitis.

RESULTS:

CMMG could only be detected in the CSF of subjects with neuropsychiatric symptoms and signs (median CMMG concentration 1.0 micromol/L, range 0.6-7.0). The concentration of CMMG was below the limit of quantification (<0.5 micromol/L) in asymptomatic subjects (P < 0.001). All patients with neuropsychiatric signs and symptoms, except one, had acute renal function impairment or chronic renal failure.

CONCLUSIONS:

These results are consistent with the hypothesis that CMMG is involved in the development of neuropsychiatric side effects in aciclovir- or valaciclovir-treated patients. Measurement of CMMG in CSF and/or serum is a promising tool in the diagnostic procedure for aciclovir- or valaciclovir-treated patients with neuropsychiatric symptoms and may help to differentiate between side effects and herpes encephalitis.

• Authors: Anders Helldén, Jan Lycke, Tatiana Vander, Jan-Olof Svensson, Ingegerd Odar-Cederlöf, Lars Ståhle
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 57 Issue 5 Pg. 945-9 (May 2006) ISSN: 0305-7453 [Print] England
• PMID: 16540518 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Guanine
• Valine
• Valacyclovir
• 9-carboxymethoxymethylguanine
• Acyclovir

Topics

• Acyclovir (adverse effects, analogs & derivatives, pharmacokinetics, therapeutic use)
• Antiviral Agents (adverse effects, pharmacokinetics, therapeutic use)
• Guanine (analogs & derivatives, cerebrospinal fluid)
• Humans
• Mental Disorders (cerebrospinal fluid, chemically induced)
• Neurotoxicity Syndromes (cerebrospinal fluid, etiology)
• Retrospective Studies
• Valacyclovir
• Valine (adverse effects, analogs & derivatives, pharmacokinetics, therapeutic use)