Pharmacokinetics of a multicomponent herbal preparation in healthy Chinese and African volunteers.
K-601 is an herbal formulation for influenza consisting of Lonicera japonica, Isatis indigotica, Rheum palmatum, Phellodendron chinense, and Scutellaria baicalensis. In this work, we characterized the chemical constituents in K-601, identified the absorbed compounds and determined their pharmacokinetics in 6 Chinese and African volunteers by liquid chromatography with time-of-flight mass spectrometry. Similarity evaluation for chromatographic fingerprint of nine different batches showed values above 0.983. Totally, 50 components were identified in K-601. Then, 15 major prototype compounds and 17 metabolites were identified in human plasma. Major metabolic pathways included glucuronidation, sulfation, methylation, demethylation, and reduction. The pharmacokinetics of the most abundant prototype compounds, berberine, jatrorrhizine, palmatine and magnoflorine were determined. Significant pharmacokinetic differences were observed between the African and Chinese subjects. The AUCs of the African is about 4-10 fold higher than that of the Chinese for the three benzylisoquinoline alkaloids. Magnoflorine, an aporphine alkaloid, was absorbed better in the Chinese than in the African. The biotransformation of K-601 by human intestinal microflora was also investigated. The major reactions included hydroxylation, methylation, demethylation, acetylation and reduction. Glucuronidation and sulfation were not observed with fecal flora. These results may be important and useful in linking data from pharmacological assays and clinical effects.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, No.24 Tongjia Lane, Nanjing 210009, China.
Raphael N
RN
Alolga
State Key Laboratory of Natural Medicines, China Pharmaceutical University, No.24 Tongjia Lane, Nanjing 210009, China.
Yong
Y
Fan
Nanjing Children's Hospital Affiliated to Nanjing Medical University, No.72, Guangzhou Road, Nanjing 210029, China.
Gang
G
Zhang
State Key Laboratory of Natural Medicines, China Pharmaceutical University, No.24 Tongjia Lane, Nanjing 210009, China.
Jin
J
Li
State Key Laboratory of Natural Medicines, China Pharmaceutical University, No.24 Tongjia Lane, Nanjing 210009, China.
Yi-Jing
YJ
Zhao
State Key Laboratory of Natural Medicines, China Pharmaceutical University, No.24 Tongjia Lane, Nanjing 210009, China.
Jimmy
J
Lelu Kakila
Department of Emergency Center, the First Affiliated Hospital of Nanjing Medical University, No. 300 Guangzhou Road, Nanjing 210029, China.
Yan
Y
Chen
State Key Laboratory of Natural Medicines, China Pharmaceutical University, No.24 Tongjia Lane, Nanjing 210009, China.
Ping
P
Li
State Key Laboratory of Natural Medicines, China Pharmaceutical University, No.24 Tongjia Lane, Nanjing 210009, China.
Lian-Wen
LW
Qi
D000328:Adult; D000470:Alkaloids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001060:Aporphines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D044466:Asian People; D044182:Benzylisoquinolines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D001599:Berberine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics; D001600:Berberine Alkaloids / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D044383:Black People; D002851:Chromatography, High Pressure Liquid; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage / Q000493:pharmacokinetics*; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D021241:Spectrometry, Mass, Electrospray Ionization
D000470:Alkaloids; D001060:Aporphines; D044182:Benzylisoquinolines; D001600:Berberine Alkaloids; D004365:Drugs, Chinese Herbal; C055785:jatrorrhizine; D001599:Berberine; C005413:palmatine; C001670:magnoflorine