Effect of commonly used vehicles on gastrointestinal, renal, and liver function in rats.
BACKGROUND
Solubility is often a limiting factor when testing new compounds in animal experiments. Various solubilizing agents may be used, but each have their own pharmacological effects. We investigated the effects of selected vehicles having different chemical characteristics on gastrointestinal, renal, and liver function.


METHODS
Rats were treated orally, intravenously or intraperitoneally and gastric emptying, intestinal transit, renal, and liver function were investigated.


RESULTS
Gastrointestinal motility was influenced by hydroxyethylcellulose, hydroxypropyl-beta-cyclodextrin (HPbetaCD), HPgammaCD, DMSO, polyethylene glycol 400 (PEG 400), fat emulsion, and the corresponding emulsifier. Liver function was affected by HPbetaCD, HPgammaCD, DMSO, PEG 400, Polysorbate 80, Cremophor RH 40, and fat emulsion. An increase in liver enzymes was observed after PEG 400 and Polysorbate 80. DMSO interfered with clinical chemistry measurements in serum. Urinary function was modified by HPgammaCD, DMSO, PEG 400, and Polysorbate 80, while enhanced urine enzyme excretion was observed after HPbetaCD, HPgammaCD, DMSO, PEG 400, and Polysorbate 80.


CONCLUSIONS
Most of the investigated vehicles changed gastrointestinal, renal, and/or liver parameters after application of a certain threshold dose for each assay. No "best" vehicle could be identified that may be used in each test system. Thus, vehicles must be selected not only on their chemical characteristics but also on their potential pharmacological activity in a given test system.
Group General Pharmacology, Drug Discovery Support, Boehringer Ingelheim Pharma GmbH & Co. KG, D-88397 Biberach an der Riss, Germany. S.Pestel@bc.boehringer-ingelheim.com
Sabine
S
Pestel
Hans-Juergen
HJ
Martin
Gerd-Michael
GM
Maier
Brian
B
Guth
D000818:Animals; D002482:Cellulose / Q000031:analogs & derivatives / Q000494:pharmacology; D003505:Cyclodextrins / Q000494:pharmacology; D004064:Digestive System / Q000187:drug effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004798:Enzymes / Q000097:blood; D005079:Excipients; D005217:Fat Emulsions, Intravenous / Q000494:pharmacology; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects; D005772:Gastrointestinal Transit / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008099:Liver / Q000187:drug effects*; D008111:Liver Function Tests; D008297:Male; D014677:Pharmaceutical Vehicles / Q000494:pharmacology*; D011092:Polyethylene Glycols / Q000494:pharmacology; D011136:Polysorbates / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012997:Solvents
D003505:Cyclodextrins; D004798:Enzymes; D005079:Excipients; D005217:Fat Emulsions, Intravenous; D014677:Pharmaceutical Vehicles; D011136:Polysorbates; D012997:Solvents; D011092:Polyethylene Glycols; D002482:Cellulose; C002283:hydroxyethylcellulose; D004121:Dimethyl Sulfoxide