title: Simultaneous in vivo RP-HPLC-DAD quantification of multiple-component and drug-drug interaction by pharmacokinetics, using 6,7-dimethylesculetin, geniposide and rhein as examples.
abstract: Increasing evidence has demonstrated that multidrug combinations could amplify the therapeutic efficacies of each agent. Interestingly, the pharmacological effect of traditional Chinese medicine (TCM) is usually attributed to the drug-interaction property (synergism) of multiple active constituents. Pharmacokinetics is a useful means of evaluating the drug interactions of major active compounds in TCM. A simple, sensitive and reliable RP-HPLC-DAD method has been developed to simultaneously quantify 6,7-dimethylesculetin (D), geniposide (G) and rhein (R), which are the active ingredients in Yin-Chen-Hao-Tang (YCHT), performing drug-interaction pharmacokinetics studies in vivo. Plasma samples were prepared using methanolic precipitation, a filtration step, and then injection of the methanolic extract onto a Nova-Pak C₁₈ Guard-Pak™ guard column with a gradient mobile phase. Triple-wavelength diode array detection was set at λ(max) values of 343 nm for D, 241 nm for the G, and 259 nm for R. Our results successfully demonstrate that this method has excellent and satisfactory selectivity, sensitivity, linearity, precision, accuracy and recovery. In healthy rats, the estimated pharmacokinetic parameters (i.e. C(max) , AUC and Cl) of D, G and R, when administered with COC (a combination of D, G and R), were C(max) 16.05 mg/L, AUC 108.96 mg h/L and Cl 0.36 L/h for D; C(max) 9.35 mg/L, AUC 64.71 mg h/L and Cl 0.88 L/h for G; and C(max) 14.18 mg/L, AUC 57.98 mg h/L and Cl 1.77 L/h for R. Here, we report that the COC combination could significantly increase the plasma level and slow the elimination rate compared with any one or two of the three individual compounds, which may indicate a drug-drug interaction.
authors: National TCM Key Laboratory of Serum Pharmacochemistry, Heilongjiang University of Chinese Medicine, and Ministry of Education, Heping Road 24, Harbin 150040, China.
authors: Aihua
authors: A
authors: Zhang
authors: Hui
authors: H
authors: Sun
authors: Xijun
authors: X
authors: Wang
authors: Guozheng
authors: G
authors: Jiao
authors: Ye
authors: Y
authors: Yuan
authors: Wenjun
authors: W
authors: Sun
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D056148:Chromatography, Reverse-Phase / Q000379:methods; D003374:Coumarins / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D004357:Drug Synergism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D039823:Iridoids / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D016014:Linear Models; D008297:Male; D008956:Models, Chemical; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000880:Anthraquinones; D003374:Coumarins; D004365:Drugs, Chinese Herbal; D039823:Iridoids; C007835:geniposide; C018145:scoparone; C020491:rhein