Anesthetic profile of a non-lipid propofol nanoemulsion.
OBJECTIVE
The clinical use of a lipid propofol formulation causes pain during injection, allergic reactions, and bacterial growth. Propofol has been reformulated in different non-lipid presentations to reduce the incidence of adverse effects, but those changes can modify its pharmacokinetics and pharmacodynamics. In the present study, we investigate the pharmacology and toxicology of lipid propofol (CLP) and the non-lipid nanoemulsion (NLP).


METHODS
Conventional lipid formulation of propofol and NLP were infused in the jugular veins of rats and blood pressure (BP), heart rate (HR), and respiratory rate (RR) were measured. Both formulations (1%) were infused (40 μL.min⁻¹) over 1 hour. Hypnotic and anesthetic doses as well as recoveries were determined. The pain induced by the CLP and NLP vehicles was compared by counting the number of abdominal contortions ("writhing test") after the intraperitoneal (i.p.) injection in mice. Acetic acid (0.6%) was used as positive control.


RESULTS
Hypnotic and anesthetic doses of 1% CLP (6.0 ± 1.3 and 17.8 ± 2.6 mg.kg⁻¹, respectively) and 1% NLP (5.4 ± 1.0 and 16.0 ± 1.4 mg.kg⁻¹, respectively) were not significantly different. Recovery from hypnosis and anesthesia was faster with NLP than with CLP. Changes in HR, BP, and RR caused by NLP were not significantly different from those caused by CLP. Acetic acid and the vehicle of CLP caused 46.0 ± 2.0 and 12.5 ± 0.6 abdominal contortions 20 min after i.p. injection, respectively. The absence of abdominal contractions was observed with the vehicle of NLP. Abdominal inflammatory response was not observed after the i.p. injection of both propofol vehicles.


CONCLUSIONS
Non-lipid formulation of propofol can be a better alternative to CPL for intravenous anesthesia with fewer adverse effects.
Sudo
Roberto Takashi
RT
Program of Drug Development, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro. rtsudo@farmaco.ufrj.br
Bonfá
Laura
L
Trachez
Margarete Manhães
MM
Debom
Roberto
R
Rizzi
Marisa D R
MD
Zapata-Sudo
Gisele
G
D018686:Anesthetics, Intravenous / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D004655:Emulsions; D008297:Male; D051379:Mice; D049329:Nanostructures; D015742:Propofol / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
D018686:Anesthetics, Intravenous; D004655:Emulsions; D015742:Propofol