Comparison of in vivo nephrotoxicity in the rabbit by a pyrrolidinyl-thio Carbapenem CW-270031.
CW-270031 is a novel synthesized carbapenem antibiotic with a broad antimicrobial activity. Carbapenem antibiotics are well known for their nephrotoxicity. In this study, we evaluated the nephrotoxicity potential of this compound in rabbits, which are known for being more sensitive than other animals to renal insult. CW-270031 was administered to NZW male rabbits via an ear vein (200 mg/kg, single injection). Blood samples were collected on 2, 3, and 4 days after treatment. Urea nitrogen and creatinine in plasma were quantified. Four days after the treatment, all animals were autopsied and histopathological examinations were performed on their kidneys, revealing that cephaloridine and imipenem were highly nephrotoxic, and cefazolin had mild renal toxicity, whereas CW-270031 as well as meropenem and tienam had no toxicity to the kidney. The present findings suggest that CW-270031 is a potential carbapenem antibiotic with no nephrotoxicity.
Kim
Jong Myung
JM
Department of Microbiology, Kyungpook National University, Daegu 702-701, Korea.
Ha
Jong Ryul
JR
Oh
Se Woong
SW
Kim
Hong Gi
HG
Lee
Jin Man
JM
Kim
Byung Oh
BO
Lee
Dong Geun
DG
Lee
Sang-Han
SH
Kim
Jong Guk
JG
D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D015780:Carbapenems / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D015377:Cilastatin / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D015378:Imipenem / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry; D007668:Kidney / Q000187:drug effects* / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced*; D008297:Male; D000077731:Meropenem; D011759:Pyrrolidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000737:chemistry; D011817:Rabbits; D013845:Thienamycins / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D011759:Pyrrolidines; D013845:Thienamycins; D015377:Cilastatin; D015378:Imipenem; D000077731:Meropenem