Cardiopulmonary side-effects and pharmacokinetics of an emulsion of propofol (Disoprivan) in comparison to propofol solved in polysorbate 80 in goats.
The aim of this study was to determine whether any pharmacokinetic or pharmacodynamic differences exist in goats between propofol in its currently licensed form (Disoprivan) and a new 1% solution of propofol (NSP) containing polysorbate 80. Nine goats received, on two different occasions in a randomized double-blinded order, 4 mg/kg propofol intravenously (i.v.; Disoprivan or NSP). To detect differences in cardiopulmonary effects and pharmacokinetics, the Wilcoxon signed rank test for paired data was used. In the NSP group the duration of initial apnoea was significantly longer, and 6 and 12 min after drug application PaO2 levels were significantly lower than in the Disoprivan group. Mean cardiovascular parameters did not differ significantly between the groups but in the NSP group in six goats marked changes in blood pressure occurred: systolic arterial pressures fell to a minimum of 40-60 mmHg within the first 10 min. This was followed by a marked increase in blood pressure, with maxima exceeding 300 mmHg. In the NSP group the half-life of propofol was significantly longer, the clearance rate was smaller and the areas under the drug concentration-time curves were larger than in the Disoprivan group. The cardiopulmonary side-effects of NSP suggest that propofol dissolved in polysorbate 80 is not a suitable alternative to the current formulation of propofol.
Bettschart-Wolfensberger
R
R
Veterinär-Chirurgische Klinik, Universität Zürich, Switzerland.
Semder
A
A
Alibhai
H
H
Demuth
D
D
Aliabadi
F S
FS
Clarke
K W
KW
D018686:Anesthetics, Intravenous / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D000818:Animals; D019540:Area Under Curve; D001784:Blood Gas Analysis / Q000662:veterinary; D001794:Blood Pressure; D004311:Double-Blind Method; D004655:Emulsions / Q000008:administration & dosage; D005079:Excipients / Q000008:administration & dosage; D005260:Female; D006041:Goats / Q000502:physiology*; D006207:Half-Life; D006339:Heart Rate; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D011136:Polysorbates / Q000008:administration & dosage; D015742:Propofol / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics*; D011897:Random Allocation; D012996:Solutions; D013997:Time Factors
D018686:Anesthetics, Intravenous; D004655:Emulsions; D005079:Excipients; D011136:Polysorbates; D012996:Solutions; D015742:Propofol