Elevated glycemia and local inflammation after injecting N-methyl-2-pyrrolidone (NMP) into the marginal ear vein of rabbits.
The objective of this pilot study was to evaluate glycemia in rabbits by administering various vehicles for solubilizing poorly soluble candidate drugs used for the treatment of diabetes. Groups of three New Zealand White rabbits received intravenously: saline; 2.0 IU/kg insulin; 23 to 45% dimethyl acetamide (DMA)/10% cremophor (v:v) in water; or N-methyl-2-pyrrolidone (NMP). For the determination of glycemia, blood was collected just before and 0.25, 0.5, 1, 2, 4, and 24 h after injection. Glycemia after saline and DMA/cremophor injections remained stable and within the normal range (3.6 to 5.0 mmol/l). In insulin-injected rabbits, glycemia decreased (1 to 2 mmol/l) as expected. With NMP, glycemia was elevated (7.8 mmol/l), and animals were hyperactive upon injections. Injected ears gradually became bluish; 48 h after injection, they were edematous and necrotic. In conclusion, DMA/cremophor seems to be an acceptable vehicle. However, NMP may cause stress and local ear irritation when injected intravenously in rabbits.
Moreau
J P
JP
Phoenix International Life Sciences, 2350 Cohen, Ville Saint-Laurent, Montreal, Quebec, H4R 2N6, Canada.
Vachon
P J
PJ
Huneau
M C
MC
D000818:Animals; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000662:veterinary; D004195:Disease Models, Animal; D004423:Ear / Q000294:innervation* / Q000473:pathology; D006943:Hyperglycemia / Q000139:chemically induced* / Q000662:veterinary; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007249:Inflammation / Q000139:chemically induced / Q000662:veterinary; D007275:Injections, Intravenous; D008297:Male; D009336:Necrosis; D011760:Pyrrolidinones / Q000008:administration & dosage / Q000009:adverse effects*; D011817:Rabbits; D012995:Solubility; D013723:Teratogens / Q000633:toxicity*
D007004:Hypoglycemic Agents; D011760:Pyrrolidinones; D013723:Teratogens; C038678:N-methylpyrrolidone