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The effect of ciprofloxacin on antipyrine metabolism
Abstract:
The effect of multiple-dose ciprofloxacin on antipyrine metabolism was studied in patients suffering from bacterial infections. The patients were given antipyrine 15 mg/kg intravenously before and after ciprofloxacin treatment. The dosage of ciprofloxacin was 500 mg bd by mouth for 8-10 days. Blood samples were taken at 0, 2, 4, 6, 10 h. Antipyrine total clearance was significantly decreased after ciprofloxacin treatment (0.85 +/- 0.45 vs. 0.52 +/- 0.24 ml/min/kg): elimination rate constants for antipyrine were decreased in all patients after ciprofloxacin, whereas no change in volume of distribution was observed. The average half-life of antipyrine was increased from 9.45 +/- 3.74 h to 14.92 +/- 3.32 h. In two males with advanced chronic hepatic failure the antipyrine half-lives were extremely prolonged. Our results support the hypothesis that ciprofloxacin inhibits intrinsic hepatic drug-metabolizing capacity and may be a source of clinically important drug interactions, particularly in patients with liver disease.
Insights
Multiple-dose ciprofloxacin significantly slows down antipyrine metabolism in patients with bacterial infections. This drug interaction may be more severe in individuals with liver disease.
Area of Science:
- Pharmacology
- Drug Metabolism
- Clinical Pharmacy
Background:
- Antipyrine is a model drug used to assess hepatic drug-metabolizing capacity.
- Ciprofloxacin is a broad-spectrum antibiotic commonly prescribed for bacterial infections.
Purpose of the Study:
- To investigate the impact of multiple-dose ciprofloxacin on the metabolism of antipyrine.
- To evaluate the potential for drug interactions between ciprofloxacin and antipyrine.
Main Methods:
- Patients received intravenous antipyrine before and after an 8-10 day course of oral ciprofloxacin (500 mg twice daily).
- Blood samples were collected over 10 hours post-antipyrine administration to measure drug levels.
- Pharmacokinetic parameters, including total clearance, elimination rate constant, volume of distribution, and half-life of antipyrine, were calculated.
Main Results:
- Ciprofloxacin treatment significantly decreased antipyrine total clearance (0.85 +/- 0.45 vs. 0.52 +/- 0.24 ml/min/kg).
- Antipyrine elimination rate constants decreased, and average half-life increased from 9.45 +/- 3.74 h to 14.92 +/- 3.32 h.
- Extremely prolonged antipyrine half-lives were observed in two patients with advanced chronic hepatic failure.
Conclusions:
- Ciprofloxacin inhibits intrinsic hepatic drug-metabolizing enzymes.
- Clinically significant drug interactions may occur between ciprofloxacin and other drugs metabolized by the liver.
- Caution is advised when using ciprofloxacin in patients with pre-existing liver conditions due to increased risk of drug interactions.