Diazepam serum concentration-sedative effect relationship in patients with liver disease.

Sedative effects and drug elimination characteristics after intravenous bolus administration of diazepam 0.15 mg/kg were investigated in 15 patients with liver disease (Group I), and in 15 normal patients (Group II) during diagnostic laparoscopy. Diazepam induced heavier sedation in patients with liver disease (P < 0.02). Serum concentration of diazepam 30 minutes after administration was significantly lower in Group I (group with liver disease) when compared with Group II (control group) (210.68 +/- 112.65 ng/ml vs 451.57 +/- 239.87 ng/ml, p < 0.02). The sedation scores during the laparoscopy procedures correlate negatively with serum benzodiazepine levels. The benzodiazepine concentration-time profiles of the groups vary significantly (p < 0.02). Heavier sedative effect and lower benzodiazepine concentrations in patients with liver diseases suggests that the permeability of blood brain barrier increases and that higher affinity to benzodiazepine receptors exists. Differences in concentration-time courses of diazepam in patients with liver diseases is a warning indicating the accumulation of the drug when infused or used frequently.