Herb-drug interaction: The effect of Polygonum capitatum extract on pharmacokinetics of levofloxacin in rats

Polygonum capitatum is a traditional medicinal plant of the Miao people and has been used to treat a variety of urological disorders in China for many years. Preparations made from water-soluble P. capitatum extracts, Relinqing® granules, are often used in combination with levofloxacin to treat urinary tract infections, and have demonstrated better clinical efficacy than either drug alone. As there is no information on the pharmacokinetics of both drugs after co-administration, a sensitive and reliable ultra-performance liquid chromatography-tandem mass spectrometry method was developed and validated to study the potential herb-drug interactions between P. capitatum and levofloxacin. This analytical method delivered high levels of specificity, recovery, accuracy, precision and preserved sample stability. When applied to study pharmacokinetic interactions after oral co-administration of P. capitatum extract (1.86 g kg−1) and levofloxacin (42 mg kg−1) in rats, the results indicated significant reductions in Cmax and AUC0−24h of levofloxacin, and significant increases in MRT, Tmax, CLz/F and Vz/F. Moreover, pretreatment with P. capitatum extract orally did not alter the intravenous pharmacokinetics of levofloxacin. Combined and compared oral pharmacokinetic parameters, suggesting that the interacting targets might localized in the intestine during absorption. Overall, the results revealed a potential herb-drug interaction between P. capitatum and levofloxacin.