Pharmacokinetics of midazolam in anaesthetized cirrhotic patients

The pharmacokinetics of midazolam were compared in cirrhotic patients (n = 10) and control patients (n = 9), during general anaesthesia. Total plasma clearance was 637 +/- 223 ml min-1 (mean +/- SD) in control patients and 402 +/- 170 ml min-1 in cirrhotic patients (P less than 0.05). The total volume of distribution was similar. Elimination half-life was 135 +/- 40 min in controls and 168 +/- 30 min in cirrhosis (P less than 0.05). Protein binding was evaluated by equilibrium dialysis in both groups at two concentrations of midazolam: 20 and 500 micrograms litre-1. No saturation occurred, but the free fraction was 4.9 +/- 1.7% in cirrhotic patients, compared with 1.9 +/- 0.6% in controls (P less than 0.01). Despite its mainly hepatic elimination, midazolam disposition appears to be only slightly impaired in cirrhotic patients.