High serum concentrations of the acyclovir main metabolite 9‐carboxymethoxymethylguanine in renal failure patients with acyclovir‐related neuropsychiatric side effects: an observational study

Background. Acyclovir (ACV) has been used for over two decades to treat herpes virus infections. Serious neurological adverse side effects have occurred during ACV treatment in patients with renal failure, but the cause of the symptoms remains unknown. We hypothesized that increased concentrations of the ACV main metabolite 9‐carboxymethoxymethylguanine (CMMG) correlated to these symptoms. Methods. We conducted an observational study from 1991 to mid 1999 based on samples sent for analysis of ACV concentration from various hospital departments in Sweden. Patients with neuropsychiatric symptoms (NS+, n=49) were compared with patients without symptoms (NS−, n=44). ACV and CMMG concentrations were analysed by HPLC. Medical records were analysed for symptoms and compared with pertinent cases identified from Medline. Results. The serum CMMG levels were significantly higher in the NS+ group (mean=34.1 µmol/l, 95% confidence interval 23.4–46.1) compared with the NS− group (mean=4.7 µmol/l, 95% confidence interval 3.3–6.6; P