External validation of pharmacokinetic and pharmacodynamic models of microemulsion and long‐chain triglyceride emulsion propofol in beagle dogs

Abstract

Lee, S.‐H., Park, H.‐W., Kim, M.‐J., Noh, M.‐H., Yoon, H.‐S., Choi, B.‐M., Lee, E.‐K., Noh, G.‐J. External validation of pharmacokinetic and pharmacodynamic models of microemulsion and long‐chain triglyceride emulsion propofol in beagle dogs. J. vet. Pharmacol. Therap. 35 , 329–341. This study aimed at assessing the predictive performance of a target‐controlled infusion (TCI) system, which incorporates canine PK–PD models for microemulsion and long‐chain triglyceride emulsion (LCT) propofol and at investigating time independency of propofol effect on the observed electroencephalographic approximate entropy (ApEn) in TCI. Using a crossover design with a 7‐day washout period, 28 healthy beagle dogs were randomized to receive TCI of both formulations in a stepwise or constant manner. Plasma propofol concentrations and ApEn were measured at preset intervals. Pooled biases, inaccuracies, divergences, and wobbles in pharmacokinetic and pharmacodynamic predictions were 2.1% (95% CI: −0.8 to 4.9), 18.1% (15.6–20.5), 1.9%/h, 7.3% (5.4–9.3), and −0.5% (−2.6 to 1.6), 8.7% (7.3–10.1), 2.5%/h, 6.0% (4.1–7.2) for microemulsion propofol, and −9.3% (−11.6 to −6.9), 20.1% (18.2–22.0), 5.1%/h, 7.6% (6.1–9.1) and 5.6% (4.1–7.1), 8.0% (6.9–9.3), 4.7%/h, 4.1% (3.1–5.1) for LCT propofol. Observed ApEn values over time were statistically not different across all time points in a TCI with constant manner. Canine PK–PD model of microemulsion propofol showed good predictive performances. Propofol effect (ApEn) was time independent as long as time is allowed for equilibration.