Poloxamer 188 as vehicle for injectable diazepam.
The significant occurrence of thrombophlebitis in patients administered diazepam intravenously was described recently. This side effect has been attributed to the crystallization of diazepam and its subsequent precipitation upon contact with blood or intravenous fluids. The current study was designed to reveal whether the solubilizing capability of poloxamer 188 reduces the incidence of thrombotic and inflammatory effects of diazepam in rabbits. The incidence of early (3-hr) ear vein necrosis was 72% in the diazepam-treated ears, while the incidence of necrosis in the ears that received poloxamer 188 as a vehicle for diazepam was 25%. The occurrence of thrombosis and loss of vessel integrity also was higher in diazepam-treated ears than in those treated with diazepam plus poloxamer 188. Solubilization of diazepam with poloxamer 188 may decrease the incidence of the tested side effects.
D000818:Animals; D003975:Diazepam / Q000008:administration & dosage*; D007267:Injections; D008297:Male; D009336:Necrosis / Q000139:chemically induced; D014677:Pharmaceutical Vehicles; D011060:Poloxalene / Q000009:adverse effects; D011092:Polyethylene Glycols / Q000009:adverse effects; D011817:Rabbits; D013924:Thrombophlebitis / Q000139:chemically induced; D013927:Thrombosis / Q000139:chemically induced
D014677:Pharmaceutical Vehicles; D011092:Polyethylene Glycols; D011060:Poloxalene; D003975:Diazepam