Pancreatic concentrations of cefepime in experimental necrotizing pancreatitis.
To evaluate the penetration of cefepime in the inflamed pancreas, three doses of 50 mg/kg were administered intramuscularly at 8-h intervals after induction of acute necrotizing pancreatitis using intraperitoneal injection of DL-ethionine in 35 rabbits and in 33 controls. Animals were sacrificed and concentrations of cefepime were determined by a microbiological assay. Cefepime reached its peak concentrations 60 min after the last drug dose when mean values of 46.05 microg/ml, 22.34 microg/g and 34.74 microg/ml were found in serum, pancreas and bile, respectively, in rabbits with acute necrotizing pancreatitis and 45.19 microg/ml, 12.68 microg/g and 20.77 microg/ml respectively in controls. Tissue/serum ratios of cefepime were 0.48, 0.23, 0.15 and 0.09 at 60, 90, 120 and 180 min, respectively, after the last dose of cefepime in rabbits with acute necrotizing pancreatitis and 0.28, 0.18, 0.16 and 0.16, respectively at 60, 90, 120 and 180 min in controls. It is concluded that the administration of cefepime in rabbits with acute necrotizing pancreatitis resulted in pancreatic tissue levels well above the MIC90s of the common pathogens involved in pancreatic superinfection, so that its administration might be proposed for the therapy of superinfection following acute necrotizing pancreatitis in humans.
Papagoras
D
D
Department of Surgery, Sismanoglion General Hospital, Maroussi Attikis, Greece.
Giamarellos-Bourboulis
E J
EJ
Kanara
M
M
Douridas
G
G
Paraskevopoulos
I
I
Antzaklis
G
G
Karayannacos
P
P
Giamarellou
H
H
D000818:Animals; D000963:Antimetabolites / Q000008:administration & dosage / Q000009:adverse effects; D000077723:Cefepime; D002511:Cephalosporins / Q000008:administration & dosage / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005001:Ethionine / Q000008:administration & dosage / Q000009:adverse effects; D007273:Injections, Intramuscular; D008297:Male; D019283:Pancreatitis, Acute Necrotizing / Q000188:drug therapy* / Q000662:veterinary; D011817:Rabbits; D014018:Tissue Distribution
D000963:Antimetabolites; D002511:Cephalosporins; D000077723:Cefepime; D005001:Ethionine