Sustained elevated plasma aprotinin concentration in mice following intraperitoneal injections of w/o emulsions incorporating aprotinin.
This study was initiated to test the feasibility of w/o emulsions as a sustained release system for aprotinin following intraperitoneal injection in mice. The emulsion was well tolerated in mice and sustained release was observed over a period of 96 h. The time for maximum plasma concentration of aprotinin was 10 min and 12 h after injection of a control solution and the emulsion dosage form, respectively. Furthermore, the hemolytic activity of the emulsion constituents was low indicating a low acute toxicological potential of the emulsion. The present study also showed that the lipolytic activity in peritoneal exudate from mice is important for the clearance of oily vehicles from the peritoneal cavity with lipolytic rate constants ranging from 50 to 130 nmol free fatty acid released/min/mg exudate protein at 37 degrees C, pH 8.5. It was concluded that the w/o emulsion was well suited to provide sustained elevated plasma aprotinin concentrations in mice.
Department of Pharmaceutics, The Royal Danish School of Pharmacy, Universitetsparken 2, DK-2100, Copenhagen, Denmark.
S
S
Bjerregaard
L
L
Wulf-Andersen
R W
RW
Stephens
L
L
Røge Lund
C
C
Vermehren
I
I
Söderberg
S
S
Frokjaer
D000818:Animals; D007611:Aprotinin / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D019540:Area Under Curve; D002470:Cell Survival; D004655:Emulsions; D004912:Erythrocytes / Q000187:drug effects; D005122:Exudates and Transudates / Q000378:metabolism; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007274:Injections, Intraperitoneal; D008049:Lipase / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010316:Particle Size; D015842:Serine Proteinase Inhibitors / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D012995:Solubility; D014407:Tumor Cells, Cultured; D014783:Viscosity
D004655:Emulsions; D015842:Serine Proteinase Inhibitors; D007611:Aprotinin; D008049:Lipase