title: Acyclovir-induced neurotoxicity: concentration-side effect relationship in acyclovir overdose.
abstract: OBJECTIVE
  To investigate the concentration-side effect relationship in a patient with severe acyclovir-induced neurotoxicity and to summarize the information available in the literature about central nervous system side effects due to acyclovir.
  
  
  METHODS
  Repeated blood samples were drawn in a patient with severe acyclovir overdose who developed coma and nonoliguric renal failure. The acyclovir levels measured by radioimmunoassay were related to the level of consciousness.
  
  
  RESULTS
  We measured the highest acyclovir serum levels reported so far (229.9 mumol/L = 51.8 mg/L). Impairment of consciousness developed with a remarkable temporal delay of 24 to 48 hours after occurrence of peak serum concentrations and resolved with a comparable delay after reaching the therapeutic range (anticlockwise hysteresis). Six days after discontinuation of the drug, central nervous system symptoms had resolved, and, 4 days later, renal function returned to pretreatment values.
  
  
  CONCLUSIONS
  The observation that neurotoxicity developed with a delay of 24 to 48 hours after acyclovir peak serum concentrations could explain the wide range of acyclovir levels reported in similar cases. Single drug level measurements may therefore be of little diagnostic value. Since toxicity develops with a remarkable delay, early removal of the drug (by hemodialysis) could possibly prevent central nervous toxicity.
authors.affiliation: Department of Internal Medicine, University Hospital (Kantonsspital), Basel, Switzerland.
authors.forename: W E
authors.initials: WE
authors.lastname: Haefeli
authors.forename: R A
authors.initials: RA
authors.lastname: Schoenenberger
authors.forename: P
authors.initials: P
authors.lastname: Weiss
authors.forename: R F
authors.initials: RF
authors.lastname: Ritz
mesh_terms: D000212:Acyclovir / Q000097:blood / Q000506:poisoning*; D000368:Aged; D001921:Brain / Q000187:drug effects*; D062787:Drug Overdose; D004569:Electroencephalography / Q000187:drug effects; D005260:Female; D006563:Herpes Zoster Ophthalmicus / Q000188:drug therapy; D006801:Humans; D007668:Kidney / Q000187:drug effects; D013997:Time Factors; D014474:Unconsciousness / Q000139:chemically induced*
chemical_list: D000212:Acyclovir