Integrated pharmacokinetic study of multiple effective components contained in total Panax notoginsenosides

Aim: This study was designed to develop and validate a novel integrated pharmacokinetic approach to assessing the holistic pharmacokinetic properties of traditional Chinese medicines(TCM). Methods: Concentrations of panax notoginsenoside R1, ginsenoside Rg1, Rd, Re and Rb1 in rat plasma were determined by robust LC-ESI-MS method after intragastric and intravenous administration of 300 and 10 mg·kg^-1 dosage of TPNs, respectively. Pharmacokinetic parameters of each compound were calculated using DAS software. A novel approach of self-defined weighting coefficient based on the area under the curve from zero to infinity (AUC_0-∞) has been created to obtain the holistic pharmacokinetic profiles of TPNs. The integrated pharmacokinetic parameters of TPNs were then calculated from both typical compartment and non-compartmental model analysis. Results: TPNs was rapidly absorbed in rats after intragastric administration of 300 mg·kg^-1 TPNs. Pharmacokinetic parameters showed great differences between 20(s)-protopanaxadiol and 20(s)-protopanaxatriol after both iv. and ig. administration. The t_{1/ 2} of for Rb1 and Rd were significantly longer than that for Rg1, Re, and R1. Based on the self-defined AUC weighting coefficients integration approach, the holistic pharmacokinetic profiles for both ig and iv. dosage were obtained, from which the integrated pharmacokinetic parameters were calculated. The holistic t_1/2 and AUC_0-∞ were of 18.88 h, 25.33 mg·h·L^-1 for ig dosage and of 22.04 h, 84.83 mg·h·L^-1 for iv. dosage. Conclusion: A novel integrated pharmacokinetic approach tn describing the holistic pharmacokinetic properties of TCM has been successfully developed and validated using TPNs as a model herbal medicine. This study would be useful for guiding the holistic pharmacokinetic study in consistence with the intrinsic theory and characteristics of traditional Chinese medicine.