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Planta Med 2013; 79(16): 1552-1557
DOI: 10.1055/s-0033-1350832
Pharmacokinetic Investigations
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Metabolism and Excretion of Kakkalide and Its Metabolites in Rat Urine, Bile, and Feces as Determined by HPLC/UV and LC/MS/MS

Hong Wang   *
1   Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, China
,
Xue Bai   *
1   Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, China
,
Jiahong Sun
2   Department of Pharmacology, University of North Texas Health Science Center, Fort Worth, Texas, USA
,
Yoshihiro Kano
1   Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, China
,
Toshiaki Makino
3   Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan
,
Dan Yuan
1   Department of Traditional Chinese Medicine, Shenyang Pharmaceutical University, Shenyang, China
› Author Affiliations
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Publication History

received 09 January 2013
revised 15 August 2013

accepted 19 August 2013

Publication Date:
09 October 2013 (online)

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Abstract

This study investigated the metabolic fate of kakkalide (irisolidone 7-xylosylglucoside), a major isoflavone found in extracts of Pueraria lobata flowers, and in rat urine, bile, and feces. Using HPLC/UV or LC/MS/MS methods, seven metabolites, tectorigenin-7-O-glucuronide, tectorigenin-7-O-sulfate, tectorigenin-4′-O-sulfate, 6-OH biochanin A-glucuronide, irisolidone-7-O-glucuronide, tectorigenin, and irisolidone were identified in rat urine after oral administration of kakkalide. Furthermore, irisolidone-7-O-glucuronide was found in bile, and irisolidone and kakkalide were found in feces. An HPLC/UV method for simultaneous quantification of all the metabolites and kakkalide in urine, bile, and feces was developed using daidzein or apigenin as the internal standard. Over a 72-h period, 13.2 ± 2.8 % of the kakkalide was excreted as seven metabolites in urine. Over the same time period, irisolidone-7-O-glucuronide excretion in bile accounted for 3.8 ± 1.1 % of the dose, while kakkalide and irisolidone excretion in feces accounted for 2.1 ± 0.7 % and 0.7 ± 0.1 % of the dose, respectively. The results indicate that urine is the primary route of kakkalide elimination in vivo and that extensive metabolism may be one of the reasons for the low bioavailability of kakkalide.

Key words

kakkalide - Pueraria lobata - Leguminosae - excretion - pharmacokinetics - conjugate metabolites - rat

* These authors contributed equally to this work.


Supporting Information

 

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