Placental transfer of enrofloxacin and ciprofloxacin in rabbits

Jose J. Aramayona From the Departments of Pharmacology and Physiology (Aramayona, Fraile, Abadia, Bregante) and Analytical Chemistry (Garda), Faculty of Veterinary, University of Zaragoza, Zaragoza 50013, Spain.

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Maria A. Garcia From the Departments of Pharmacology and Physiology (Aramayona, Fraile, Abadia, Bregante) and Analytical Chemistry (Garda), Faculty of Veterinary, University of Zaragoza, Zaragoza 50013, Spain.

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Lorenzo J. Fraile From the Departments of Pharmacology and Physiology (Aramayona, Fraile, Abadia, Bregante) and Analytical Chemistry (Garda), Faculty of Veterinary, University of Zaragoza, Zaragoza 50013, Spain.

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Ana R. Abadía From the Departments of Pharmacology and Physiology (Aramayona, Fraile, Abadia, Bregante) and Analytical Chemistry (Garda), Faculty of Veterinary, University of Zaragoza, Zaragoza 50013, Spain.

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Miguel A. Bregante From the Departments of Pharmacology and Physiology (Aramayona, Fraile, Abadia, Bregante) and Analytical Chemistry (Garda), Faculty of Veterinary, University of Zaragoza, Zaragoza 50013, Spain.

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Summary

Placental transfer of enrofloxacin and ciprofloxacin was evaluated, using a rabbit in situ perfusion model. A two-step infusion program was carried out to obtain steady-state maternal plasma concentrations of these drugs. For each compound, the placenta in 5 rabbits was perfused for 200 minutes with Earle's enriched bicarbonate buffer at flow rate of 1.5 ml/min. To assess reliability of the model, most of the determinants of placental transfer (maternal and fetal pH, gas balance, heart status, rectal temperature, and protein binding) were controlled. In addition, the infusion program included administration of antipyrine, a commonly used indicator of placental exchange.

Drug concentrations were measured in maternal plasma and perfusate by use of a high-performance liquid chromatographic assay. Plasma protein-binding estimation indicated no differences between the drugs. Placental clearance of the drugs was significantly (P< 0.01) different (0.88 ± 0.13 ml/min for enrofloxacin and 0.06 ± 0.02 ml/min for ciprofloxacin). These values accounted for 81 and 5%, respectively, of the placental clearance found for antipyrine.

These results indicate that caution must be taken when enrofloxacin is to be used during pregnancy, and suggest the need to extend this type of experiment to species that can be exposed to these drugs used for therapeutic or prophylactic purposes.

Summary

Placental transfer of enrofloxacin and ciprofloxacin was evaluated, using a rabbit in situ perfusion model. A two-step infusion program was carried out to obtain steady-state maternal plasma concentrations of these drugs. For each compound, the placenta in 5 rabbits was perfused for 200 minutes with Earle's enriched bicarbonate buffer at flow rate of 1.5 ml/min. To assess reliability of the model, most of the determinants of placental transfer (maternal and fetal pH, gas balance, heart status, rectal temperature, and protein binding) were controlled. In addition, the infusion program included administration of antipyrine, a commonly used indicator of placental exchange.

Drug concentrations were measured in maternal plasma and perfusate by use of a high-performance liquid chromatographic assay. Plasma protein-binding estimation indicated no differences between the drugs. Placental clearance of the drugs was significantly (P< 0.01) different (0.88 ± 0.13 ml/min for enrofloxacin and 0.06 ± 0.02 ml/min for ciprofloxacin). These values accounted for 81 and 5%, respectively, of the placental clearance found for antipyrine.

These results indicate that caution must be taken when enrofloxacin is to be used during pregnancy, and suggest the need to extend this type of experiment to species that can be exposed to these drugs used for therapeutic or prophylactic purposes.

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