Majallah-i Dānishgāh-i ̒Ulūm-i Pizishkī-i Bābul (Jun 2009)
Effect of Erythromycin on the Intestinal Transport of Cyclosporine
Abstract
BACKGROUND AND OBJECTIVE: Co-administration of cyclosporine and erythromycin can cause nephrotoxicity which could be a result of interaction in absorption and/or metabolism level. The purpose of this work was to investigate the interaction of erythromycin and cyclosporine in absorption level to evaluate the effect of erythromycin on cyclosporine absorption quantitatively. The stability of drug at 37°C and its adsorption to plastic syringe and tubes were also investigated.METHODS: 32 Wistar rats weighting between 200-300 g were used in the present study. They were divided into 4 test groups and 4 control groups. A jejunal segment of anaesthetized rat was cannulated and perfused by concentrations of 20, 15, 10 and 5 micromolar of drug in the presence and absence of 150 micromolar erythromycin by flow rate of 0.2 ml/min. Samples were obtained up to 90 min. Drug concentrations were assayed in different time points. The drug effective permeability values were calculated for its different concentrations in different experiments. A reverse-phase HPLC method was used for analysis of all samples.FINDINGS: The cyclosporine effective permeability values were increased from 22.1-33.4 (×10-6) cm/sec in control group to 37.2-53.4 (×10-6) cm/sec in test group that this difference was significant (p<0.05). Moreover cyclosporine was stable and only 4-5% loss of drug was observed at the end of experiment. However there was a significant adsorption of drug to syringe and tubing.CONCLUSION: Based on obtained results cyclosporine is a low solubility and high permeability drug. At least some part of clinical interaction between cyclosporine and erythromycin is due to interaction in absorption level.
