Current Issue : July - September Volume : 2018 Issue Number : 3 Articles : 6 Articles
Ziyuglycoside I (ZGS1) is a promising drug candidate for the treatment of leucopenia.\nCurrently, information on ZGS1 and its in vivo metabolite ziyuglycoside II (ZGS2) is limited.\nThe objective of this study was to investigate the pharmacokinetics, tissue distribution, and excretion\nof ziyuglycoside I (ZGS1) and its metabolite ziyuglycoside II (ZGS2) in rats. In our study, a simple\nand sensitive high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method\nwas established for simultaneous determination of ZGS1 and its metabolite for Sprague-Dawley rat\npharmacokinetics studies. The method was validated following internationally-approved guidelines.\nThe results presented in this study indicated that subcutaneous administration of ZGS1 prolonged\nits extension time and increased the area under the curve (AUC0ââ?¬â??t) of ZGS2 during 0 to t minutes.\nIn summary, in this study, the pharmacokinetic characteristics of ZGS1 and its metabolite ZGS2\nwere defined and its tissue distribution, and excretion in rats were described. Our finding may be\nbeneficial for leucopenia drug that focus on ZGS1....
Objectives. To determine whether the pharmacokinetic parameters of Gd-EOB-DTPA can identify the difference in liver function\nin a rat hepatectomy model. Methods. A total of 56 eight-week-old male Sprague-Dawley rats were divided into the following\ngroups: control group without hepatectomy (...
Apium graveolens (celery) is an edible and traditionally medicinal plant that is used\nworldwide, among others for the treatment of hypertension. Combining celery with antihypertensive\ndrugs can affect the pharmacodynamics and pharmacokinetics of the latter drugs. The aim of the\nstudy is to assess the effects of administrating the celery extract on captopril pharmacokinetics.\nSprague-Dawley strain rats were divided into two groups (n = 6). Group I was given captopril\n(10 mg/kg Body Weight (BW)) orally, while Group II was pretreated with celery extract orally\n(40 mg/kg BW) an hour before administration of captopril. The blood samples were withdrawn\nat various intervals after drug administration. The captopril concentration was determined using\nliquid chromatographyââ?¬â??mass spectrometry (LC-MS/MS) and from the blood data, the values of Ke,\nCmax, Tmax, T1/2, and area under the curve (AUC) were calculated. The results showed that oral\nadministration of the celery extract increased Cmax (38.67%), T1/2 (37.84%), and AUC (58.10%) and\ndecreased Ke (27.45%) of captopril in Group II (celery + captopril) compared with Group I (captopril).\nIn conclusion, celery extract can alter the pharmacokinetic of captopril when given in combination.\nThe combination might be beneficial for the treatment of hypertension, as celery causes an increase in\nthe plasma level of captopril, which can enhance its efficacy...
Fucus vesiculosus L., known as bladderwrack, belongs to the brown seaweeds, which are\nwidely distributed throughout northern Russia, Atlantic shores of Europe, the Baltic Sea, Greenland,\nthe Azores, the Canary Islands, and shores of the Pacific Ocean. Fucoidan is a major fucose-rich\nsulfated polysaccharide found in Fucus (F.) vesiculosus. The pharmacokinetic profiling of active\ncompounds is essential for drug development and approval. The aim of the study was to evaluate the\npharmacokinetics and tissue distribution of fucoidan in rats after a single-dose oral administration.\nFucoidan was isolated from F. vesiculosus. The method of measuring anti-activated factor X (anti-Xa)\nactivity by amidolytic assay was used to analyze the plasma and tissue concentrations of fucoidan.\nThe tissue distribution of fucoidan after intragastric administration to the rats was characterized,\nand it exhibited considerable heterogeneity. Fucoidan preferentially accumulates in the kidneys\n(AUC0ââ?¬â??t = 10.74 Ã?¼gÃ?·h/g; Cmax = 1.23 Ã?¼g/g after 5 h), spleen (AUC0ââ?¬â??t = 6.89 Ã?¼gÃ?·h/g; Cmax = 0.78 Ã?¼g/g\nafter 3 h), and liver (AUC0ââ?¬â??t = 3.26 Ã?¼gÃ?·h/g; Cmax = 0.53 Ã?¼g/g after 2 h) and shows a relatively long\nabsorption time and extended circulation in the blood, with a mean residence time (MRT) = 6.79 h.\nThe outcome of this study provides additional scientific data for traditional use of fucoidan-containing\nplants and offers tangible support for the continued development of new effective pharmaceuticals\nusing fucoidan....
The objective of this work is to evaluate the potential effect of cardiac stress exercise on the\naccumulation of [123I]IAZA, a radiopharmaceutical used to image focal tissue hypoxia, in otherwise\nnormal myocardium in healthy volunteers, and to determine the impact of exercise on [123I]IAZA\npharmacokinetics. The underlying goal is to establish a rational basis and a baseline for studies\nof focal myocardial hypoxia in cardiac patients using [123I]IAZA. Three healthy male volunteers\nran the ââ?¬Ë?Bruceââ?¬â?¢ treadmill protocol, a clinically-accepted protocol designed to expose myocardial\nischemia in patients. The ââ?¬Ë?Bruceââ?¬â?¢ criterion heart rate is 85% of [220ââ?¬â??age]. Approximately one minute\nbefore reaching this level, [123I]IAZA (5.0 mCi/0.85 mg) was administered as a slow (1ââ?¬â??3 min) single\nintravenous (i.v.) injection via an indwelling venous catheter. The volunteer continued running for\nan additional 1 min before being transferred to a gamma camera. Serum samples were collected\nfrom the arm contralateral to the administration site at pre-determined intervals from 1 min to 45 h\npost injection and were analyzed by radio HPLC. Pharmacokinetic (PK) parameters were derived for\n[123I]IAZA and total radioactivity (total[123I]) using compartmental and noncompartmental analyses.\nWhole-body planar scintigraphic images were acquired from 0.75 to 24 h after dosing. PK data and\nscintigraphic images were compared to previously published [123I]IAZA data from healthy volunteers\nrest. Following exercise stress, both [123I]IAZA and total[123I] exhibited bi-exponential decline profiles,\nwith rapid distribution phases [half-lives (t1/2Ã?±) of 1.2 and 1.4 min, respectively], followed by slower\nelimination phases [t1/2Ã?² of 195 and 290 min, respectively]. Total body clearance (CLTB) and the steady\nstate volume of distribution (Vss) were 0.647 L/kg and 185 mL/min, respectively, for [123I]IAZA\nand 0.785 L/kg and 135 mL/min, respectively, for total[123I]. The t1/2Ã?², CLTB and Vss values were\ncomparable to those reported previously for rested volunteers. The t1/2Ã?± was approximately 4-fold\nshorter for [123I]IAZA and approximately 3-fold shorter for total[123I] under exercise relative to rested\nsubjects. The heart region was visualized in early whole body scintigraphic images, but later images\nshowed no accumulated radioactivity in this region, and no differences from images reported for\nrested volunteers were apparent. Minimal uptake of radiotracer in myocardium and skeletal muscle\nwas consistent with uptake in non-stressed myocardium. Whole-body scintigrams for [123I]IAZA in\nexercise-stressed healthy volunteers were indistinguishable from images of non-exercised volunteers.\nThere was no evidence of hypoxia-dependent binding in exercised but otherwise healthy myocardium,\nsupporting the conclusion that exercise stress at Bruce protocol intensity does not induce measurable\nmyocardial hypoxia. Effects of exercise on PK parameters were minimal; specifically, the t1/2Ã?± was\nshortened, reflecting increased cardiac output associated with exercise. It is concluded that because\n[123I]IAZA was not metabolically bound in exercise-stressed myocardium, a stress test will not create elevated myocardial background that would mask regions of myocardial perfusion deficiency.\n[123I]IAZA would therefore be suitable for the detection of viable, hypoxic myocardium in patients\nundergoing stress-test-based diagnosis....
Physiologically based pharmacokinetic modelling (PBPK) is a powerful tool to predict in vivo pharmacokinetics based on\nphysiological parameters and data from in vivo studies and in vitro assays. In vivo PBPK modelling in laboratory animals by\nnoninvasive imaging could help to improve the in vivo-in vivo translation towards human pharmacokinetics modelling. We\nevaluated the feasibility of PBPKmodellingwith PET data frommice.We used data fromtwo of our PET tracers under development,\n[11C]AM7 and [11C]MT107. PET images suggested hepatobiliary excretion which was reduced after cyclosporine administration.\nWe fitted the time-activity curves of blood, liver, gallbladder/intestine, kidney, and peripheral tissue to a compartment model and\ncompared the resulting pharmacokinetic parameters under control conditions ([11C]AM7 ...
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