We previously demonstrated that i.v. emulsified isoflurane induces general anaesthesia in animals. In this study, we compared the pharmacokinetics of emulsified isoflurane given as i.v. bolus and as infusion in beagle dogs.Methods
Sixteen beagle dogs were assigned randomly to a bolus group comprising three subgroups and an infusion group. The three bolus subgroups received 120, 150, or 180 mg kg−1 of isoflurane and the infusion group received isoflurane at 12 mg kg−1 min−1 for 150 min. Isoflurane concentrations were determined by gas chromatography. The parameters involved in the pharmacokinetic model were calculated using the DAS ver1.0 software.Results
A two-compartment model best described the data in both bolus and infusion groups. The half-lives of distribution [t1/2α: 1.77 (0.57) min] and elimination [t1/2β: 17.66 (5.56) min] in the bolus group were shorter than those in the infusion group [14.12 (4.04) min, 58.21 (11.39) min, P<0.01]. The apparent volume of the central compartment [V1, 0.377 (0.138) litre kg−1] in the bolus group was less than that in the infusion group [0.809 (0.077) litre kg−1, P<0.01]. The total body clearance [Cl, 0.043 (0.032) litre kg−1 min−1] in the bolus group was greater than that in the infusion group [0.028 (0.008) litre kg−1 min−1].Conclusions
A two-compartment model adequately describes the pharmacokinetics of emulsified isoflurane for both bolus and infusion. The resulting kinetic parameters differ mainly because of the increasing blood/gas partition coefficient and the sustained nature of the isoflurane partial pressure during infusion.