Current Issue : October - December Volume : 2018 Issue Number : 4 Articles : 5 Articles
Microdialysis, a sampling method for pharmacokineticsââ?¬â??pharmacodynamics (PKââ?¬â??PD)\nmodeling in preclinical and clinical studies, is a convenient in vivo sampling technique. Geniposide\n(GE), an iridoid glycoside compound, is the major active ingredient of Gardenia jasminoides Ellis fruit\nwhich has an anti-inflammatory effect. In this study, an articular cavity microdialysis sampling system\nfor adjuvant arthritic (AA) rats was established to study the effect of GE on the release of prostaglandin\nE2 (PGE2) in AA rats induced by Freundââ?¬â?¢s complete adjuvant (FCA). An UHPLC-MS/MS method\nwas developed to determine the concentrations of GE and PGE2 in the dialysate. Through the\ndetermination of drug concentrations and PGE2 efficacy levels in the dialysate, the developed\nmethods were successfully applied to set up concentrationââ?¬â??time and effectââ?¬â??time profiles followed\nby PKââ?¬â??PD modeling of GEââ?¬â?¢s effect on decreasing PGE2 release after oral administration of GE.\nThe effect was well described by the developed PKââ?¬â??PD modeling, indicating that GE may play an\nanti-inflammatory role via decreasing AA-induced elevated PGE2 levels. In the selection of suitable\nendogenous small molecules as effect markers, the establishment of AA rat joint-cavity microdialysis\nis an attractive technique for rational PKââ?¬â??PD studies....
The Raw Curcumae Rhizoma (R-CR), included in the Chinese Pharmacopoeia Edition 2015, is a well-known Chinese herbal\nmedicine. However, the vinegar-processed Curcumae Rhizoma (V-CR) is used more widely than R-CR. The pharmacokinetics\ncomparison of R-CR and V-CR after oral administration to rats is poorly understood. A novel method, rapid resolution liquid\nchromatography-tandem mass spectrometry (RRLC-MS) coupled with a sensitive, specific, and convenient microdialysis sampling\nmethod, free fromendogenous interference was developed in this research.The extracts of R-CR andV-CRwere administered orally\nto each group of rats.The blood and liver microdialysis probes were positioned within the jugular vein toward the right atrium and\nthe median lobe near the center of the liver, respectively. Then, a double-peak phenomenon was observed in the concentrationtime\ncurves of curdione in R-CR group, while it was not observed in V-CR group. The liver-to-blood distribution ratio of curdione\nin V-CR group increased significantly (...
This study developed the pharmacokinetic (PK)ââ?¬â??pharmacodynamic (PD) model of the\ntestosterone-suppressive effect of leuprolide for evaluation of the sustained release (SR) depot and\nleuprolide solution in rats with or without prostate cancer. Six groups of rats were divided by the\nroutes of administration (intravenous and subcutaneous injection) and kinds of formulation (vehicle,\nleuprolide solution, and SR depot). The PK profile after subcutaneous injection of leuprolide solution\ncould be well-described by the one-compartment model. The absorption rate constant, the total body\nclearance, and the volume of distribution were estimated at 16.67 hâË?â??1, 514.46 mL/h, and 487.40 mL.\nUsing PK parameters in the solution-administered group, the PK model for the SR depot was\ndeveloped. The PKââ?¬â??PD model was constructed by describing the testosterone-suppressive effect of\nleuprolide using the feedback turnover model. The response of testosterone after administration of\neach formulation was well described using this PKââ?¬â??PD model for the estimation of PD parameters\n(EC50, Emax, h) and systemic parameters (kin, kout, kf on, kf off). The developed PKââ?¬â??PD model containing\nan inhibitory feedback system could successfully describe the testosterone-suppressive effect of\nleuprolide in the type of formulation. The PKââ?¬â??PD model developed would be useful for evaluating\nthe formulation of similar drugs whose effect is regulated through the feedback mechanism....
Background. Bojungikki-tang (BJIKT) is a widely used traditional herbal formula in China, Japan, and Korea. There have been\nreports that several herbs among BJIKT have interactions with antiplatelet drugs, such as aspirin. This study aimed to assess\nwhether BJIKT interacts with aspirin in terms of pharmacokinetics (PK) and pharmacodynamics (PD) in healthy subjects and\nischemic stroke patients. Methods.The phase I interaction trial was a randomized, open-label, crossover study of 10 healthy male\nsubjects, and the phase III interaction trial was a randomized, placebo-controlled, parallel study of 43 ischemic stroke patients.\nEach participant randomly received aspirin + BJIKT or aspirin + placebo. For PK analysis, plasma acetyl salicylic acid (ASA) and\nsalicylic acid (SA) were evaluated, and, for PD analysis, platelet aggregation and plasma thromboxane B2 (TxB2) were measured.\nResults. In the PK parameters, mean area under curve, maximum concertation, and peak concentration time of ASA and SA were\nnot different between two groups in healthy subjects and ischemic stroke patients. In the PD profiles, TxB2 concentrations and\nplatelet aggregation were not affected by coadministration of BJIKT in healthy subjects and ischemic stroke patients. Conclusions.\nThese results suggest that coadministration of BJIKT with aspirin may not result in herb-drug interaction....
Carbapenemase-producing Klebsiella pneumoniae is globally recognized as one of the greatest threats to public health, and\ncombination therapy may be the chemotherapeutic option. In the present study, we aimed to evaluate the antibacterial effects of\ncolistin/fosfomycin combination against carbapenemase-producing K. pneumoniae.The antibacterial effects were determined in a\none-compartment in vitro pharmacokinetic model over a period of 24 h.The initial inoculumwas 108 CFU/mL. Low, medium, and\nhigh...
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