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

ObjectiveTo 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 designProspective, randomized, blinded experimental trial.AnimalsNinety-six adult laboratory rabbits, mean ± SD weight 2.20 ± 0.15 kg.MethodsStage 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 F_2h, F_4h, F_6h, F_8h and P_2h, P_4h, P_6h, P_8h. 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 (propofol_F) and propofol emulsion were measured with respect to loss and recovery of RR and TCS.ResultsMIR 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, F_2h 15 ± 3; F_4h 26 ± 4; F_6h 52 ± 6; F_8h 84 ± 10; and P_2h 10 ± 1; P_4h 19 ± 7; P_6h 36 ± 7; P_8h 48 ± 5.Conclusions and clinical relevanceAfter 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.