Disposition of sanguinarine in the rat

Abstract

Sanguinarine is an alkaloid with known antibiotic and anti-inflammatory activity and its pharmacokinetics have been studied in the rat after a single oral dose (10 mg kg⁻¹ body weight). Alkaloid determination in the plasma and liver was carried out by high-performance liquid chromatography–electrospray ionization mass spectrometry (HPLC/ESI-MS). The pharmacokinetic parameters (t_max, c_max, AUC_0→t and AUC_0→∞) were determined for sanguinarine and dihydrosanguinarine, the major components detected in plasma. The first step in sanguinarine metabolism in the rat was the reduction of the iminium bond resulting in formation of the less toxic dihydrosanguinarine. Both compounds were completely eliminated from the plasma and liver after 24 h and not detected in urine. After a single oral dose of ³H-sanguinarine, more than 42% of the ingested radioactivity was present in gastrointestinal tract. Benz[c]acridine, up to date the only sanguinarine metabolite referred to in the literature, was not detected in the plasma, liver or urine.

Key Words::

• Sanguinarine
• dihydrosanguinarine
• pharmacokinetics
• biodistribution

Acknowledgements

This work was supported by the Grant Agency of the Czech Republic (GA ČR 525/07/0871) and by the Czech Ministry of Education through the MSM6198959216 project. We thank M. Hřebíčková and Ing. Š. Pšondrová for technical assistance in the synthesis of ³H-sanguinarine.