Multiple dose kinetics of ketobemidone in surgical patients.

Twelve patients scheduled for major abdominal surgery were selected for a study of the kinetics of ketobemidone during the day of surgery and in a follow-up study 3-5 days after surgery. In six patients ketobemidone was administered as ketobemidone plain and in the other six, it was given as Ketogin, a combination formula containing a spasmolytic substance in addition to ketobemidone. Plasma samples were collected for approximately 24 h following induction of anesthesia, during which time multiple doses of ketobemidone were administered. A single-dose study was performed 3-5 days after surgery using the same drug. No significant differences were found between the two formulations of ketobemidone. Plasma clearance did not change significantly between the two periods of study, being 18.0 +/- 4.4 ml . kg-1 . min-1 peroperatively and 21.7 +/- 7.6 ml . kg-1 . min-1 postoperatively. Peroperative Vd area was significantly larger than post-operative Vd area, 5.84 +/- 2.62 l . kg-1 and 3.63 +/- 0.38 l . kg-1, respectively. T1/2 terminal decreased from 3.84 +/- 1.6 h peroperatively to 2.06 +/- 0.44 h postoperatively.