Famotidine-associated central nervous system reactions and plasma and cerebrospinal drug concentrations in neurosurgical patients with renal failure.

Central nervous system toxicity of H2-receptor antagonists has rarely been confirmed by the respective elevated cerebrospinal fluid drug concentrations. We observed two hemodialyzed neurosurgical patients in whom mental deterioration and convulsions developed after intravenous famotidine therapy (10 and 40 mg/day). Their cerebrospinal fluid drug concentrations were grossly elevated (i.e., 160 and 249 ng/ml) compared with those obtained from three other hemodialyzed neurosurgical patients who exhibited no central nervous system reactions (i.e., 47 to 85 ng/ml). In addition, the mean cerebrospinal fluid/plasma drug concentration ratio obtained from these five neurosurgical patients with renal failure (i.e., 0.46) and that from 10 other neurosurgical patients with normal renal function (i.e., 0.41) were about four times greater than that previously reported from non-neurosurgical patients with normal renal function (i.e., 0.12). Our observation suggests that patients with not only renal dysfunction but also following neurosurgical operations have an excessive accumulation of famotidine in the central nervous system and are more susceptible to the drug-induced adverse central nervous system reactions.