Acute intoxication of cyclosporin caused by coadministration of decoctionsof the fruits of Citrus aurantium and the pericarps of Citrus grandis

In order to investigate the effects of Citrus herbs on cyclosporin absorpti on and disposition, swine were given cyclosporin (10 mg/kg) with or without decoctions of Citri Aurantii Fructus (CAF) or Citri Grandis Pericarpium (C GP) in a crossover design. FPIA method (fluorescence polarization immunoass ay) was used to determine the blood concentration of cyclosporin. The decoc tions were characterized by their flavanone contents. Our results indicated that the coadministration of CAF and CGP significantly increased the C-max of cyclosporin by 64% and 79%, respectively. The AUC of cyclosporin was si gnificantly elevated by 97% when coadministered with CGP. Among the swine, 1/5 and 3/5 exhibited acute toxicity of cyclosporin after concomitant intak e of CAF and CGP, respectively. This indicates an interaction of Citrus com pounds with a commonly used drug. We suggest when cyclosporin is coadminist ered with these Citrus decoctions, the blood concentration of cyclosporin s hould be carefully monitored for dose adjustment to avoid cyclosporin intox ication.