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Biliary elimination of cefotiam, an experimental and clinical study
Abstract:
Five isolated rabbit livers were in vitro perfused over a 3-hour period. After addition of 10 mg of cefotiam to the circulating blood, a biliary peak concentration of 76.2 +/- 14.2 micrograms/ml (mean +/- SEM) was reached between the 90th and 120th min; 3.1 +/- 0.4% of the dose given was excreted in the bile during the 3-hour period. In 10 recently cholecystectomized patients provided with a T-tube drain, 1 g of cefotiam was given intravenously. A biliary peak concentration of 340 +/- 81 micrograms/ml was observed 2 h later. 1.8 +/- 0.7% of the administered dose was recovered in the bile during the 12-hour period. In 5 clinically normal subjects given intravenously 1 g of cefotiam, 0.5 +/- 0.2% of the administered dose was found in the duodenal fluid aspirated over a 4-hour period. Cefotiam concentrations measured in choledochal and gallbladder bile collected simultaneously during operation 1 h after intravenous administration of 1 g of the drug to 10 patients were 502 +/- 102 micrograms/ml and 143 +/- 39 micrograms/ml, respectively; they exceeded significantly the concentration determined in the serum sampled at the same time (17.9 +/- 2.6 micrograms/ml). The biliary parameters of cefotiam were compared with those of 14 other beta-lactam antibiotics previously studied by the same procedure. The results of the present study are consistent with a possible beneficial effect of cefotiam in the treatment of biliary tract infections.
Insights
Cefotiam demonstrates significant biliary excretion in rabbits and humans, suggesting potential efficacy for treating biliary tract infections. This cephalosporin antibiotic achieves high concentrations in bile, exceeding serum levels.
Area of Science:
- Pharmacology
- Hepatobiliary Medicine
- Infectious Diseases
Background:
- Biliary tract infections (BTIs) require effective antibiotic treatment.
- Understanding antibiotic penetration into bile is crucial for BTI management.
- Cefotiam is a cephalosporin antibiotic with potential applications in BTIs.
Purpose of the Study:
- To evaluate the biliary excretion and concentration of cefotiam in preclinical and clinical models.
- To compare cefotiam's biliary pharmacokinetics with other beta-lactam antibiotics.
- To assess the potential of cefotiam for treating biliary tract infections.
Main Methods:
- In vitro perfusion of isolated rabbit livers with cefotiam.
- Intravenous administration of cefotiam to cholecystectomized patients with T-tube drains.
- Intravenous administration of cefotiam to healthy subjects with duodenal fluid aspiration.
- Simultaneous collection of bile (choledochal and gallbladder) and serum during surgery.
- Comparison of cefotiam's biliary parameters with 14 other beta-lactam antibiotics.
Main Results:
- In rabbits, cefotiam reached a peak biliary concentration of 76.2 µg/ml, with 3.1% of the dose excreted in bile over 3 hours.
- In humans, intravenous cefotiam achieved peak biliary concentrations of 340 µg/ml (T-tube) and 502 µg/ml (choledochal bile), with 1.8% dose recovery over 12 hours.
- Bile concentrations of cefotiam significantly exceeded serum concentrations (502 µg/ml vs. 17.9 µg/ml).
- Minimal cefotiam was found in duodenal fluid (0.5% of dose over 4 hours) in healthy subjects.
Conclusions:
- Cefotiam exhibits substantial biliary excretion and achieves high concentrations in bile in both animal models and human subjects.
- The drug's pharmacokinetic profile in bile supports its potential clinical utility in treating biliary tract infections.
- Cefotiam's biliary penetration is favorable compared to other studied beta-lactam antibiotics.