Pharmacokinetics of thiopentone: effects of enflurane and nitrous oxide anaesthesia and surgery.

Plasma concentrations of thiopentone following the injection of 3.5 mg kg-1 i.v. were studied in six patients who received enflurane and nitrous oxide anaesthesia and six volunteers. We identified a three-compartment open model system containing both a "shallow" and a "deep" peripheral compartment in all the patients and half of the controls, and a two-compartment open model for the remaining volunteers. The distribution of thiopentone to the tissues was very rapid, the alpha and beta distribution half-lives averaging 2.5 min and 46.4 min respectively for the patient group and 2.8 min and 48.7 min for the control group. The wide distribution of the drug was indicated by the apparent volume of distribution, the means of which varied between 2 and 1.5 times body weight. The mean elimination half-life was 5.1 h for the patients and 5.7 h for the volunteers. The return of the drug to the central compartment from the deep peripheral compartment was the rate-controlling factor in its elimination. Neither enflurane and nitrous oxide anaesthesia nor the stress of surgery affected the distribution or clearance of the drug from plasma.