Reply

Anders Helldén and Lars Ståhle

Karolinska Institutet Huddinge University Hospital Stockholm Sweden Email: anders.hellden{at}hs.se

Sir,

Dr Almond brings into the discussion of our data the results from several important studies of ACV pharmacokinetics in patients with reduced renal function. We are well aware of these studies. However, the simultaneous pharmacokinetics of ACV and CMMG in such circumstances is not known. There are some studies from the early 1980s showing that CMMG concentration in urine was increased in patients with renal failure, but the relation with neurological symptoms was never established [1].

The main point in our article is that CMMG serum concentrations above 11 µmol/l are associated with a risk of developing neuropsychiatric symptoms. These can develop as early as a few hours after the first dose. Although we have not established that CMMG is the cause of the symptoms, neither have we rejected that hypothesis. It is therefore of evident interest to know if minimization of CMMG levels is a way to avoid development of neuropsychiatric symptoms and this is the reason why we consider a study of CMMG and ACV simultaneous pharmacokinetics crucial.

Furthermore, it may be the case that the rate of metabolism of ACV to CMMG is individual, i.e. some patients may develop neuropsychiatric symptoms despite dose reduction aimed at achieving a given level of ACV.

It is our conclusion that an estimation of CMMG in serum, which takes a laboratory ~1 h to perform, is probably a cheaper and less risky way to prevent neuropsychiatric symptoms than to adjust the dose when the patient develops symptoms and then perform an acute haemodialysis session.

Conflict of interest statement. None declared.

References

  1. Blum MR, Liao SH, de Miranda P. Overview of acyclovir pharmacokinetic disposition in adults and children. Am J Med 1982;73: 186–192[ISI][Medline]




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