Pharmacokinetics and pharmacodynamics of propofol microemulsion and lipid emulsion after an intravenous bolus and variable rate infusion.
BACKGROUND
The aim of this trial was to evaluate the induction and recovery characteristics of microemulsion propofol (Aquafol; Daewon Pharmaceutical Co., Ltd., Seoul, Korea). Pharmacokinetics, pharmacodynamics, and safety profile were investigated. Lipid emulsion propofol (Diprivan; AstraZeneca, London, United Kingdom) was used as a comparator.


METHODS
Thirty-one healthy volunteers aged 20-79 yr were given an intravenous bolus of propofol 2 mg/kg, followed by variable rate infusion for 60 min. Each volunteer was studied twice with different formulations at an interval of 1 week. Arterial concentrations of propofol were measured, and Bispectral Index was used as a surrogate measure of propofol effect. The induction and recovery characteristics including bioequivalence were evaluated by noncompartmental analysis. The pharmacokinetics and pharmacodynamics were investigated using a population approach with mixed effects modeling. The rate, severity, and causal relation of adverse events were analyzed.


RESULTS
Both formulations were bioequivalent. The observed time to peak effect after a bolus of both formulations was 1.5 min. Plasma concentration of propofol at loss of consciousness, time to loss of consciousness after a bolus, and time to recovery of consciousness after discontinuation of infusion did not show significant differences. The population pharmacokinetics and pharmacodynamics revealed a variety of differences between two formulations. Aquafol showed similar safety profile to Diprivan.


CONCLUSIONS
The efficacy and safety of Aquafol were not different from those of Diprivan within the dose range in this study.
Kim
Kye-Min
KM
Department of Anesthesiology and Pain Medicine, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea.
Choi
Byung-Moon
BM
Park
Si-Won
SW
Lee
Soo-Han
SH
Christensen
Lane V
LV
Zhou
Jiaye
J
Yoo
Byung-Hoon
BH
Shin
Hye-Won
HW
Bae
Kyun-Seop
KS
Kern
Steven E
SE
Kang
Sung-Hong
SH
Noh
Gyu-Jeong
GJ
D000328:Adult; D000368:Aged; D018686:Anesthetics, Intravenous / Q000008:administration & dosage*; D018592:Cross-Over Studies; D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D015742:Propofol / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D012449:Safety
D018686:Anesthetics, Intravenous; D004655:Emulsions; D005217:Fat Emulsions, Intravenous; D015742:Propofol