Dataset Information

Intravenous formulation of Panax notoginseng root extract: human pharmacokinetics of ginsenosides and potential for perpetrating drug interactions.

ABSTRACT: XueShuanTong, a lyophilized extract of Panax notoginseng roots (Sanqi) for intravenous administration, is extensively used as add-on therapy in the treatment of ischemic heart and cerebrovascular diseases and comprises therapeutically active ginsenosides. Potential for XueShuanTong-drug interactions was determined; the investigation focused on cytochrome P450 (CYP)3A induction and organic anion-transporting polypeptide (OATP)1B inhibition. Ginsenosides considerably bioavailable for drug interactions were identified by dosing XueShuanTong in human subjects and their interaction-related pharmacokinetics were determined. The CYP3A induction potential was determined by repeatedly dosing XueShuanTong for 15 days in human subjects and by treating cryopreserved human hepatocytes with circulating ginsenosides; midazolam served as a probe substrate. Joint inhibition of OATP1B by XueShuanTong ginsenosides was assessed in vitro, and the data were processed using the Chou-Talalay method. Samples were analyzed by liquid chromatography/mass spectrometry. Ginsenosides Rb₁, Rd, and Rg₁ and notoginsenoside R₁ were the major circulating XueShuanTong compounds; their interaction-related pharmacokinetics comprised compound dose-dependent levels of systemic exposure and, for ginsenosides Rb₁ and Rd, long terminal half-lives (32?57 and 58?307?h, respectively) and low unbound fractions in plasma (0.8%?2.9% and 0.4%?3.0%, respectively). Dosing XueShuanTong did not induce CYP3A. Based on the pharmacokinetics and inhibitory potency of the ginsenosides, XueShuanTong was predicted to have high potential for OATP1B3-mediated drug interactions (attributed chiefly to ginsenoside Rb₁) suggesting the need for further model-based determination of the interaction potential for XueShuanTong and, if necessary, a clinical drug interaction study. Increased awareness of ginsenosides' pharmacokinetics and XueShuanTong-drug interaction potential will help ensure the safe use of XueShuanTong and coadministered synthetic drugs.

SUBMITTER: Pintusophon S

PROVIDER: S-EPMC6786404 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Intravenous formulation of Panax notoginseng root extract: human pharmacokinetics of ginsenosides and potential for perpetrating drug interactions.

Pintusophon Salisa S Niu Wei W Duan Xiao-Na XN Olaleye Olajide E OE Huang Yu-Hong YH Wang Feng-Qing FQ Li Yan-Fen YF Yang Jun-Ling JL Li Chuan C

Acta pharmacologica Sinica 20190729 10

XueShuanTong, a lyophilized extract of Panax notoginseng roots (Sanqi) for intravenous administration, is extensively used as add-on therapy in the treatment of ischemic heart and cerebrovascular diseases and comprises therapeutically active ginsenosides. Potential for XueShuanTong-drug interactions was determined; the investigation focused on cytochrome P450 (CYP)3A induction and organic anion-transporting polypeptide (OATP)1B inhibition. Ginsenosides considerably bioavailable for drug interact ...[more]

PMID: 31358899

Similar Datasets

Project description:BackgroundTo investigate the biosynthesis and pharmacokinetic course of enteric-coated soft capsules of Panax notoginseng saponins (PNS) in a beagle dog model.MethodsTo satisfy the enteric properties of soft capsules, the PNS enteric soft gelatin capsules were prepared by formaldehyde impregnation and orthogonal experimental design. The fluidity of gelatin and the disintegration time were selected as evaluation indexes; the soft gelatin capsule content was self-emulsifying, and the Km value and the optimal prescription were determined by making three-phase diagrams; in vivo pharmacokinetics studies were performed on six beagle dogs with 3 dogs in each group. Beagle dogs were divided into two groups randomly. One group was given PNS self-emulsifying enteric capsule and the other was given market conventional capsules. Plasma samples were collected at different times. After 1 week, the crossover experiment was carried out. The plasma concentration was detected by HPLC-MS (high performance liquid chromatography-mass spectrometry). Then the pharmacokinetic parameters were calculated by non-compartment model analysis.ResultsThe range and variance analysis of the orthogonal test determined that the best prescription of total saponins of Panax notoginseng enteric soft capsule was:gelatin:glycerol:water =1:1:2, Soak the films in 1% formaldehyde for 1 hour. The contents of the soft capsule self-microemulsion are prescribed as: IPM (isopropyl myristate):Cremophor RH40:PEG400 (polyethylene glycol 400) =1:4.5:4.5 (with suitable PNS); the pharmacokinetic parameters of PNS self-emulsified enteric capsules and conventional capsules in the market are as follows: Rb1:Cmax is (18.05±0.26) and (15.50±0.51) ng/mL, Tmax is (2.00±0) and (3.00±0) h, AUC0→t is 98.49±1.16 and 34.46±2.02 (ng/mL)·h, relative bioavailability is 196.2%; Rg1: Cmax is 4.16±0.25 and 3.88±0.28 ng/mL, Tmax is 2.00±0 and 1.50±0 h, area under drug time curve (AUC)0→t is 11.80±2.93 and 10.45±2.29 (ng/mL)·h, relative bioavailability is 77.2%; R1:Cmax is 1.84±0.25 and 1.48±0.21 ng/mL, Tmax is 2.08±0.49 and 1.92±0.20 h, AUC0→t is 7.06±2.07 and 7.16±2.59 (ng/mL)·h, relative bioavailability is 117.7%.ConclusionsThe experiment in vivo showed the higher relative bioavailability of PNS self-emulsifying enteric capsule compared with market conventional capsules. This will provide a potential application prospect for the clinical research and applications of PNS.

Dataset Information

Intravenous formulation of Panax notoginseng root extract: human pharmacokinetics of ginsenosides and potential for perpetrating drug interactions.

Publications

Intravenous formulation of Panax notoginseng root extract: human pharmacokinetics of ginsenosides and potential for perpetrating drug interactions.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets