Minimum infusion rates and recovery times from different durations of continuous infusion of fospropofol, a prodrug of propofol, in rabbits: a comparison with propofol emulsion

Objective To explore, in rabbits, the minimum infusion rates (MIR) required and recovery time from long duration (≤8 hours) continuous infusion of fospropofol disodium, a novel water-soluble prodrug of propofol, and compare it with propofol. Study design Prospective, randomized, blinded experimental trial. Animals Ninety-six adult laboratory rabbits, mean ± SD weight 2.20 ± 0.15 kg. Methods Stage 1. 16 rabbits were assigned to receive fospropofol disodium or propofol to measure MIR, using an up-and-down method with response to tail-clamping stimulus (TCS). Stage 2. Eighty rabbits were allocated to group F (fospropofol disodium) or group P (propofol), and further subdivided (n = 10 in each subgroup) according to infusion time (2, 4, 6 or 8 hours), to groups F2h, F4h, F6h, F8h and P2h, P4h, P6h, P8h. Fospropofol or propofol were infused, and tail clamping applied to maintain the same depth of anaesthesia until infusion was completed. Times to recover righting reflex (RR), to respond to TCS, and total recovery to different durations of continuous infusion of two anaesthetic drugs were noted. Respiratory and pulse rates and oxygen saturation were analyzed. The plasma concentrations of fospropofol disodium, the active metabolite propofol (propofolF) and propofol emulsion were measured with respect to loss and recovery of RR and TCS. Results MIR of fospropofol disodium was 2.0 mg kg−1 minute−1, and MIR of propofol was 0.9 mg kg−1 minute−1. Times in minutes to total recovery from anaesthesia in groups F and P were as follows, F2h 15 ± 3; F4h 26 ± 4; F6h 52 ± 6; F8h 84 ± 10; and P2h 10 ± 1; P4h 19 ± 7; P6h 36 ± 7; P8h 48 ± 5. Conclusions and clinical relevance After continuous intravenous infusion in rabbits (≤8 hours), fospropofol disodium and propofol both show an extension of recovery time with increasing infusion time, fospropofol disodium showing a significantly greater prolongation compared to propofol emulsion when infusion time increases to 6 and 8 hours.