General pharmacology of loracarbef in animals.
Loracarbef ((6R, 7S)-7-[(R)-2-amino-2-phenyl-acetamido]-3-chloro-8-oxo-1- azabicyclo [4.2.0]oct-2-ene-2-carboxylic acid, monohydrate, LY 163892, CAS 121961-22-6) is a carbacephem antibiotic targeted for use in the treatment of infectious disease. The potential pharmacological effects of this agent were examined on cardiovascular, respiratory, gastrointestinal, central nervous and autonomic nervous systems. Also examined were local anesthetic activity, effects on platelet aggregation, circulating blood glucose, primary antibody production, renal function, blood coagulation, ocular irritation, and the acute inflammatory response. Doses of 100, 1000, and 2000 mg/kg given by the oral route were selected for most in vivo studies. Concentrations up to 3 x 10(-3) mol/l were used in vitro. Loracarbef was essentially inactive in the tests of central and autonomic nervous system function, platelet aggregation, renal function, blood hemolysis, primary antibody production, blood coagulation, and ocular irritation. It had no local anesthetic activity. At high oral or intravenous doses, representing significant multiples of the therapeutic dose, loracarbef caused changes in gastrointestinal (decrease in gastric acid production and gastric fluid volume; increased biliary output), cardiovascular (increased mean pressure, cardiac output, heart rate, and femoral flow), blood glucose (increased glucose levels), and anti-inflammatory tests (suppressed acute inflammatory response). In summary, loracarbef exhibited minimal activity in these pharmacodynamic studies. These results indicate loracarbef has a low potential to produce adverse effects at therapeutic doses.
Shetler
T
T
Lilly Research Laboratories, A Division of Eli Lilly and Company, Greenfield, Indiana.
Bendele
A
A
Buening
M
M
Clemens
J
J
Colbert
W
W
Deldar
A
A
Helton
D
D
McGrath
J
J
Shannon
H
H
Turk
J
J
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D001786:Blood Glucose / Q000378:metabolism; D002490:Central Nervous System / Q000187:drug effects; D002511:Cephalosporins / Q000494:pharmacology*; D004064:Digestive System / Q000187:drug effects; D004285:Dogs; D006168:Guinea Pigs; D006439:Hemodynamics / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D007107:Immune System / Q000187:drug effects; D007249:Inflammation / Q000503:physiopathology; D007509:Irritants / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects; D008297:Male; D051379:Mice; D010974:Platelet Aggregation / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar
D000779:Anesthetics, Local; D000900:Anti-Bacterial Agents; D001786:Blood Glucose; D002511:Cephalosporins; D007509:Irritants; C054920:loracarbef