Plasma and intracerebral pharmacokinetics and pharmacodynamics modeling for the acetylcholine releasing effect of ginsenoside Rg1 in mPFC of Aß model rats.

Ginsenoside Rg1 is a major bioactive component of ginseng. Limited information is available regarding Rg1 concentrations in the central neural system and the corresponding relationship of plasma/intracerebral concentrations, and intracerebral effects of Rg1. Awake Aß model rats received a single subcutaneous administration of Rg1. Concentrations of unbound Rg1 and acetylcholine in the brain extracellular fluid and Rg1 in plasma were then determined. An Emax-two compartment pharmacokinetic/pharmacodynamics (PK/PD) model without effect compartment was finally obtained by evaluating three mechanism-based models. The corresponding relationship between the plasma PK and PD of Rg1 can be described as E = 119.05•C/(73.42 + C).[Formula: see text].

Pharmacokinetics of ginsenoside Rg1 in rat medial prefrontal cortex, hippocampus, and lateral ventricle after subcutaneous administration.

The present study aimed to investigate pharmacokinetics of Rg1 in rat medial prefrontal cortex (mPFC), hippocampus (HIP), and lateral ventricle (LV) after subcutaneous injection. For the first time, intracerebral pharmacokinetics of Rg1 was studied in freely moving rats by microdialysis technique. Rg1 concentrations in dialysates were detected by a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method and were revised using in vivo probe-recovery in HIP and LV. The pharmacokinetic parameters were then determined using non-compartmental models. Since the in vivo recoveries remained stable in HIP and LV during 9 h dialysis, average recoveries were used to revise dialysate concentrations. After dosing, Rg1 was soon detected in brain extracellular fluid (bECF) and cerebrospinal fluid (CSF). The elimination of Rg1 was significantly slower in mPFC than in HIP and LV, and significantly greater AUC was obtained in mPFC than in HIP. Rg1 kinetics in bECF and CSF indicate that Rg1 can go across the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB), and then immediately distribute to learning and memory-related regions in brain, which may lead to rapid pharmacological onset. There may be active transport and target-mediated disposition of Rg1 in the CNS, which need to be further clarified.

[Study on bioequivalence of domestic bambuterol capsules and imported tablets by high performance capillary zone electrophoresis].

AIM: To study bioequivalences of bambuterol and its metabolites terbutaline in 20 healthy male volunteers. METHODS: A single oral dose of domestic bambuterol capsule or imported bambuterol tablet was given according to a randomized 2-way cross-over design. The plasma bambuterol and terbutaline concentrations were determined by high performance capillary zone electrophoresis (HPCZE). RESULTS: The pharmacokinetic parameters of the capsule and tablet of bambuterol: AUC0-1 were (72 +/- 18) and (72 +/- 13) microgram.h.L-1, Cmax were (8.1 +/- 1.8) and (9.2 +/- 2.3) microgram.L-1, Tmax were (3.6 +/- 1.3) and (3.7 +/- 1.0) h, respectively; terbutaline: AUC0-t were (129 +/- 32) and (130 +/- 34) microgram.h.L-1, Cmax were (7.8 +/- 2.2) and (8.5 +/- 2.9) microgram.L-1, Tmax were (5.4 +/- 0.8) and (5.6 +/- 1.1) h, respectively. The bioavaiability of the capsule was (100 +/- 16)% (bambuterol) and (101 +/- 13)% (terbutaline). CONCLUSION: The results demonstrated that the two preparations of bambuterol and terbutaline were bioequivalent by analysis of variance, with two-one sided test at 90% confidential level.