The effect of commonly used vehicles on canine hematology and clinical chemistry values.
Drug metabolism and pharmacokinetic (DMPK) studies are an important phase in drug discovery research. Compounds are administered via the intravascular or extravascular routes to animals to calculate various pharmacokinetic parameters. An important step in this process is dissolving the novel compound in a safe vehicle. This procedure is particularly challenging for compounds that must be administered intravenously, as the solution must be clear before injection. There are no published guidelines on which vehicles, or combination of vehicles, are acceptable in a particular species, nor are there published data on the effects these vehicles have on clinical chemistry or hematology parameters, particularly in dogs. In this study, 9 vehicles commonly used at sanofi-aventis USA (propylene glycol, polyethylene glycol 400, glycofurol, hydroxypropyl Beta-cyclodextrin, dimethyl sulfoxide, N-methyl-2-pyrrolidone, dimethylacetamide, ethyl alcohol, and saline) were tested for adverse clinical reactions (such as vomiting or diarrhea) and for their effect on hematology and clinical chemistry parameters. Each vehicle was administered to a group of 8 Beagles by slow intravenous infusion, and blood was collected prior to infusion and at 24 h and 7 d postinfusion. Of 8 dogs given propylene glycol, 2 developed mild gastrointestinal signs (vomitus, diarrhea) after their infusions. None of the vehicles tested induced significant hematology or serum clinical chemistry abnormalities, nor were significant clinical signs noted after administration. We conclude that at the dose, route, and manner described, all of the vehicles tested in this study are clinically safe to use and have no acute effects on hematology or serum chemistry parameters.
Ruble
Gaye R
GR
Sanofi-aventis, Bridgewater, NJ, USA. Gaye.Ruble@sanofi-aventis.com
Giardino
Odessa Z
OZ
Fossceco
Stewart L
SL
Cosmatos
Dennis
D
Knapp
Richard J
RJ
Barlow
Norman J
NJ
D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000081:Acetamides / Q000008:administration & dosage / Q000633:toxicity; D000438:Alcohols / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D001774:Blood Chemical Analysis / Q000662:veterinary; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage / Q000633:toxicity; D004285:Dogs / Q000097:blood*; D006403:Hematologic Tests / Q000662:veterinary; D007262:Infusions, Intravenous; D008297:Male; D014677:Pharmaceutical Vehicles / Q000008:administration & dosage / Q000633:toxicity*; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000633:toxicity; D012965:Sodium Chloride / Q000008:administration & dosage / Q000633:toxicity; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000633:toxicity
D000081:Acetamides; D000438:Alcohols; D014677:Pharmaceutical Vehicles; D011760:Pyrrolidinones; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D012965:Sodium Chloride; C013959:dimethylacetamide; C038678:N-methylpyrrolidone; D004121:Dimethyl Sulfoxide