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.


METHODS
Prospective, randomized, blinded experimental trial.


METHODS
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 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.


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, 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
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.
Department of Anesthesiology and Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Rui
R
Li
Wen-sheng
WS
Zhang
Jin
J
Liu
Min
M
Tang
Ying-ying
YY
Yang
Nan-Fu
NF
Luo
D000762:Anesthesia Recovery Period; D000771:Anesthesia, Intravenous / Q000379:methods / Q000662:veterinary*; D018686:Anesthetics, Intravenous / Q000008:administration & dosage*; D000818:Animals; D004655:Emulsions; D005260:Female; D008297:Male; D011355:Prodrugs / Q000008:administration & dosage*; D015742:Propofol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D011817:Rabbits; D013997:Time Factors
D018686:Anesthetics, Intravenous; D004655:Emulsions; D011355:Prodrugs; C472965:fospropofol; D015742:Propofol