Pharmacokinetics of isoflurane uptake and disposition in piglets

Isoflurane is a cardioprotective inhalational anesthetic widely used in cardiac surgery, but prior studies focused primarily on uptake parameters. We examined both uptake and disposition in piglets using inspiratory, end-tidal, arterial, and mixed venous concentrations.

Seven piglets received a fixed inspiratory concentration of 2% isoflurane during a 2-h uptake phase, followed by a 2-h disposition phase. Inspiratory and end-tidal concentrations were measured using an infrared analyzer. Femoral arterial blood and pulmonary artery mixed venous blood were sampled to determine isoflurane concentrations via gas chromatography at 1, 3, 5, 10, 20, 30, 40, 50, 60, 80, 100, and 120 min during both uptake and disposition phases. Hemodynamic and respiratory parameters were recorded simultaneously. Body uptake and disposition rates were calculated by multiplying the difference between arterial and pulmonary artery blood concentrations by cardiac output.

The rates of isoflurane body uptake increased gradually during the initial 20 min, reaching 20.7 mL min^-1, before slowly declining to 10.5 mL min^-1 by 120 min. Continuous decreases in washout rates were observed during the subsequent disposition phase. The concentration-time curves for end-tidal, arterial blood, and pulmonary artery blood concentrations fit well with zero-order input and first-order disposition kinetics. Arterial and pulmonary artery blood concentrations were best modeled by a two-compartment system. Only 14.5% of the isoflurane accumulated during the 2-h uptake phase was eliminated during the subsequent 2-h disposition phase.

Under a fixed inspiratory isoflurane concentration, body uptake in piglets was empirically approximated by a zero-order input process over the modeled 120-min uptake interval, whereas the subsequent 2-h disposition phase followed first-order kinetics and was best described by a two-compartment pharmacokinetic model.