Midazolam Pharmacokinetics in Patients Undergoing Lung Surgery

Lee, Soo Il; Kim, Seung Su; Hwang, Gi Baeg; Lee, Jong Hwan

Abstract

BACKGROUND: The nature of operation alters the volume of distribution at steady state (Vdss) of drug. The hepatic extraction ratio of midazolam (0.3~0.7) could be influenced by hepatic blood flow (HBF), and hepatic enzyme activity. The pharmacokinetics of intravenous midazolam were determined in patients undergoing lung surgery.
METHODS
Midazolam, 0.2 mg/kg, was administered to five patients undergoing lung surgery at 30 minutes after induction of anesthesia. Anesthesia was maintained with O2-enflurane for one lung ventilation. Blood samples from artery were drawn at increasing intervals for 12 h. Plasma midazolam concentrations were measured by gas chromatography. Computer simulations of the times required for 20%, 50%, and 80% decreases in midazolam concentrations were performed.
RESULTS
A three compartment model best described the concentration versus time data. The volume of the central compartment (Vc) and volume of distribution at steady state (Vdss) were 4.3 2.8 l and 59.9 20.1 l, respectively. The elimination half-life was 3.4 2.2 h. Simulations indicate that under all the situations, the concentrations would decrease more rapidly in our patients in spite of similar Vdss and elimination half-life of patients undergoing minor gynecological surgery.
CONCLUSION
The elimination half-life was in the range of previously reported values. The shorter recovery time is apparently due to relatively faster redistrubution, and relatively greater capacity for redistribution.