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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 (C max ) 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  < 0.01). Time to reach C max  (T max ) for 7 mg·kg −1  KM was 4-fold longer in aged rats ( P  < 0.05). The area under the curve (AUC) of 7 mg·kg −1  KM was >17-fold and >43-fold higher than those of 0.28 mg·kg −1  KM in adult and aged rats, respectively ( P  < 0.01). The half-life (t 1/2 ) of 7 mg·kg −1  KM was over 4-fold longer than that of 0.28 mg·kg −1  KM in adult rats ( P  < 0.01). The t 1/2  of 1.4 and 7 mg·kg −1  KM were 1.5~2-fold longer, than that of 0.28 mg·kg −1  KM in aged rats ( P  < 0.05). The clearance rate of 7 mg·kg −1  KM was significantly lower in aged than in adult rats ( P  < 0.05). For 7.0 mg·kg −1  KM, the C max  in aged rats was higher than in adult rats during the T max  period ( P  < 0.05). In aged rats, the AUC for KM was >2.5-fold higher ( P  < 0.05) and the t 1/2  was >60% longer than in adult rats ( P  < 0.05). These results help interpret the pharmacokinetics of KM in aging-associated diseases.

frontiers in pharmacology

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