Orally Administered Koumine Persists Longer in the Plasma of Aged Rats Than That of Adult Rats as Assessed by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry

Aging leads to changes in nearly all pharmacokinetic phases. Koumine (KM), an alkaloid derived from Gelsemium elegans Benth., is effective against age-associated chronic diseases, but its dose proportionality following oral administration in aged individuals remains unknown. Herein, we established and validated a simple method that requires low sample volumes to determine KM concentration in rats using ultra-performance liquid chromatography-tandem mass spectrometry. The maximum plasma concentration (Cmax) of 7 mg·kg−1 KM was ~12-fold and ~24-fold higher than that of 0.28 mg·kg−1 KM in adult and aged rats, respectively (P 17-fold and >43-fold higher than those of 0.28 mg·kg−1 KM in adult and aged rats, respectively (P 2.5-fold higher (P 60% longer than in adult rats (P < 0.05). These results help interpret the pharmacokinetics of KM in aging-associated diseases.