Dermatotoxic effects of orally administered ciprofloxacin in sweating and nonsweating animal models

Cutan Ocul Toxicol. 2010 Dec;29(4):254-60. doi: 10.3109/15569527.2010.494325. Epub 2010 Jul 8.

Abstract

Context: Some drugs, such as ciprofloxacin (CFX), that are excreted in sweat may produce some effects/toxicities in the skin structure. In order to differentiate the dermatotoxic effects of drugs due to excretion in sweat, it is essential to perform simultaneous studies in sweating and nonsweating animal models.

Objective: To determine the dermatotoxic effects of CFX in sweating (goats) and nonsweating (rabbits) animals and to determine whether there is a relationship between dermatotoxicity and the blood CFX concentration.

Materials and methods: CFX was administered orally at the dose rate of 20 mg/kg body weight to goats (n = 16) and rabbits (n = 16) for 1 and 2 weeks, while control animals were given vehicle (water). Skin biopsies were taken after 1- and 2-week administration of CFX and processed histologically. Similarly, the CFX concentration in the plasma samples was analyzed by high-performance liquid chromatography (HPLC).

Results: Mean ± standard error (SE) epidermal thickness (μm) was 26.2 ± 0.2, 38.6 ± 2.05, and 37.8 ± 1.8 for the control, 1-week-treated, and 2-week-treated goats and 16.06 ± 2.39, 50.67 ± 6.61, and 34.03 ± .12 for the control, 1-week-treated, and 2-week-treated rabbits, respectively. Mean ± SE epidermal cell layers were 2.08 ± 0.08, 3.42 ± 0.16, and 3.25 ± 0.21 in the control, 1-week-treated, and 2-week-treated goats and 1 ± 0, 3.08 ± 0.37, and 1.83 ± 0.35 in the control, 1-week-treated, and 2-week-treated rabbits, respectively. Mean ± SE plasma concentration (μg/mL) of CFX was 0.37 ± 0.06 and 0.30 ± 0.05 in the 1- and 2-week-treated goats and 0.13 ± 0.04 and 0.14 ± 0.09 in the 1- and 2-week-treated rabbits, respectively.

Conclusion: Microscopically, increases in epidermal thickness, number of cell layers, and cell infiltration were observed in both sweating and nonsweating animals, indicating that the dermatotoxic effects may not be due to CFX excretion in sweat. No relationship was found between dermatotoxicity and blood CFX concentration in both animal models.

MeSH terms

  • Administration, Oral
  • Animals
  • Anti-Infective Agents / pharmacokinetics
  • Anti-Infective Agents / toxicity*
  • Biopsy
  • Chromatography, High Pressure Liquid
  • Ciprofloxacin / pharmacokinetics
  • Ciprofloxacin / toxicity*
  • Epidermis / drug effects*
  • Epidermis / pathology
  • Goats
  • Models, Animal
  • Rabbits
  • Sweat / chemistry
  • Sweat / drug effects*
  • Sweat / metabolism
  • Sweating / drug effects*
  • Sweating / physiology

Substances

  • Anti-Infective Agents
  • Ciprofloxacin