透析患者におけるアシクロビル代謝物CMMGのアシクロビル脳症への関与

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The administration of acyclovir (ACV) sometimes causes neurotoxicity in patients with renal failure and recent research suggests that it is caused by 9-carboxymethoxymethylguanine (CMMG), the main metabolite of ACV, rather than ACV itself. In this study, therefore, we determined whether such neurotoxicity in dialysis patients was associated with serum levels of ACV or CMMG. Between December 2000 and August 2006, we obtained serum samples from dialysis patients who had been treated with ACV for herpes zoster infections, and who had adequate data for assessment. The patients were divided into two groups : with neurotoxicity (Group A) and without neurotoxicity (Group B). Serum concentrations of ACV and CMMG were measured by HPLC and compared between the 2 groups. CMMG/ACV ratios were also compared. There were 9 subjects in Group A and 18 in Group B and subject backgrounds were similar. ACV serum concentrations were not significantly different between the two groups-median (range) 6.6 (1.1-9.9)μg/mL and 3.6 (0.5-12.1)μg/mL respectively (P=0.26). However, serum CMMG concentrations were significantly higher in Group A than in Group B-median (range) 10.4 (6.6-17.2)μg/mL and 2.4 (0.0-11.8)μg/mL respectively (P<0.001). The serum CMMG/ACV ratio was also higher in Group A than in Group B-median (range) 2.17 (0.75-10.20) and 0.64 (0.00-3.16) respectively (P<0.01). These results suggest that the development of neurotoxicity is associated with the accumulation of CMMG in the serum. The monitoring of serum CMMG concentrations could be therefore be useful for predicting neurotoxicity during ACV treatment in patients with renal failure.
日本医療薬学会の論文
2007-07-10

透析患者におけるアシクロビル代謝物CMMGのアシクロビル脳症への関与

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