title: Gentamicin nephrotoxicity: Animal experimental correlate with human pharmacovigilance outcome.
abstract: BACKGROUND
  National Agency for Food and Drugs Administration and Control (NAFDAC), which is responsible for pharmacovigilance activity in Nigeria, recently withdrew injection gentamicin 280 mg, used in the management of life-threatening and multidrug-resistant infections from circulation, due to reported toxicity. Thus, this study aimed to investigate the toxicity profile of the commonly used strengths (80 mg and 280 mg) of gentamicin on kidney using animal models.
  
  
  METHODS
  Animals were divided into five groups of 16 rats each. For rats of groups 1 and 2, gentamicin (1.14 mg/kg each group) was administered intramuscularly twice daily for 7 and 14 days, respectively, after which eight of them were sacrificed by cervical dislocation. Blood was collected via cardiac puncture and the kidneys were carefully removed and weighed immediately. The remaining eight animals were kept for reversibility study for another 7 and 14 days, respectively. For groups 3 and 4, gentamicin (4 mg/kg each group) was administered as a single daily dose for 7 and 14 days, respectively, and eight animals from the groups were subjected to reversibility study for 7 and 14 days, respectively. Group 5, the control group animals, were given 10 ml/kg distilled water for 14 days. Histopathology of the kidneys, serum creatinine levels, and antioxidant enzyme activities were investigated.
  
  
  RESULTS
  Significant increase (p ≤ 0.001) in the level of creatinine of rats administered 4.0 mg/kg for 14 days was observed compared with all other groups. Significant (p ≤ 0.001) elevations in the lipid peroxidation in all gentamicin-administered animals and acute tubular necrosis in most of the gentamicin-administered animals were observed.
  
  
  CONCLUSIONS
  Toxicity profile of gentamicin on the kidneys is dependent on both dose and duration of administration. The findings justify the decision made by NAFDAC to ban the use of high-dose inj. gentamicin 280 mg in Nigeria.
authors.affiliation: Department of Pharmacology, College of Medicine, Idi-Araba, University of Lagos, Nigeria.
authors.forename: Olufunsho
authors.initials: O
authors.lastname: Awodele
authors.forename: Oyindamola P
authors.initials: OP
authors.lastname: Tomoye
authors.forename: Neils B
authors.initials: NB
authors.lastname: Quashie
authors.forename: Kennedy I
authors.initials: KI
authors.lastname: Amagon
authors.forename: Sunday A
authors.initials: SA
authors.lastname: Ogunnowo
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000627:therapeutic use*; D003404:Creatinine / Q000378:metabolism; D005839:Gentamicins / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D060735:Pharmacovigilance; D051381:Rats
chemical_list: D000900:Anti-Bacterial Agents; D000975:Antioxidants; D005839:Gentamicins; D003404:Creatinine