Current Issue : January - March Volume : 2018 Issue Number : 1 Articles : 5 Articles
This is a comparative pharmacokinetics study of linezolid (Lzd), and two novel\noxazolidinone antibacterial agentsââ?¬â?PH027 and PH051ââ?¬â?in rabbits to determine if the discrepancy\nbetween the in vitro and in vivo activities of the novel compounds is due to pharmacokinetic factors.\nThe pharmacokinetics after IV and oral administration, plasma protein binding and tissue distribution\nfor the three compounds were compared. The elimination half-lives were 52.4 6.3, 68.7 12.1\nand 175 46.1 min for Lzd, PH027 and PH051, respectively. The oral bioavailability for Lzd, PH027\nand PH051 administered as suspension were 38.7%, 22.1% and 4.73%, which increased significantly\nwhen administered as microemulsion to 51.7%, 72.9% and 13.9%. The plasma protein binding were\n32ââ?¬â??34%, 37ââ?¬â??38% and 90ââ?¬â??91% for Lzd, PH027 and PH051. The tissue distribution for PH027 and\nPH051 in all investigated tissues were higher than that for Lzd. It can be concluded that the lower\nbioavailability of PH027 and PH051 compared to Lzd when administered as suspension is the main\ncause of their lower in vivo activity, despite their comparable in vitro activity. Differences in the other\npharmacokinetic characteristics cannot explain the lower in vivo activity. The in vivo activity of the\nnovel compounds should be re-evaluated using formulations with good oral bioavailability....
Doxorubicin (Dox) is an effective anti-cancer medication with poor oral bioavailability\nand systemic toxicities. DoxQ was developed by conjugating Dox to the lymphatically absorbed\nantioxidant quercetin to improve Doxââ?¬â?¢s bioavailability and tolerability. The purpose of this study\nwas to characterize the pharmacokinetics and safety of Dox after intravenous (IV) and oral (PO)\nadministration of DoxQ or Dox (10 mg/kg) and investigate the intestinal lymphatic delivery of\nDox after PO DoxQ administration in male Spragueââ?¬â??Dawley rats. Drug concentrations in serum,\nurine, and lymph were quantified by HPLC with fluorescence detection. DoxQ intact IV showed a\n5-fold increase in the area under the curve (AUC)ââ?¬â?18.6 1.98 compared to 3.97 0.71 g * h/mL\nafter Doxââ?¬â?and a significant reduction in the volume of distribution (Vss): 0.138 0.015 versus\n6.35 1.06 L/kg. The fraction excreted unchanged in urine (fe) of IV DoxQ and Dox was ~5% and\n~11%, respectively. Cumulative amounts of Dox in the mesenteric lymph fluid after oral DoxQ\nwere twice as high as Dox in a mesenteric lymph duct cannulation rat model. Oral DoxQ increased\nAUC of Dox by ~1.5-fold compared to after oral Dox. Concentrations of -N-Acetylglucosaminidase\n(NAG) but not cardiac troponin (cTnI) were lower after IV DoxQ than Dox. DoxQ altered the\npharmacokinetic disposition of Dox, improved its renal safety and oral bioavailability, and is in part\ntransported through intestinal lymphatics....
We evaluated pharmacokinetics (PK) and pharmacodynamics (PD) induced by new formulations of tramadol (TR) in\nthermoreversible gels. The poloxamer- (PL-) tramadol systems were prepared by direct dispersion of the drug in solutions with\nPL 407 and PL 188. The evaluated formulations were as follows: F1: TR 2% in aqueous solution and F2: PL 407 (20%) + PL 188 (10%)\n+ TR 2%; F3: PL 407 (25%) + PL 188 (5%) + TR 2%; F4: PL 407 (20%) + TR 2%. New Zealand White rabbits were divided into\nfour groups (...
Naoxintong capsule (NXTC) was a famous patent medicine of Traditional Chinese Medicine (TCM) to treat cerebrovascular\ndiseases in China. An LC-MS/MS method was developed for simultaneous determination of 11 major ingredients (paeoniflorin,\necdysterone, amygdalin, mulberroside A, caffeic acid, ferulic acid, salvianolic acid B, astragaloside IV, formononetin, cryptotanshinone,\nand tanshinone IIA) in NXTC in rat plasma. All analytes were separated on an Eclipse plus C18 column using a gradient\nmobile phase system of acetonitrile-0.1% formic acid aqueous solution. The lower limits of quantification of 11 ingredients were\nbetween 0.075 and 10 ngmLâË?â??1.The precision was less than 15% and the accuracies were between 85% and 115%. The results showed\nthat caffeic acid, ferulic acid, formononetin, cryptotanshinone, and tanshinone IIA could be detected after oral administration of\nNXTC. The validated method was successfully applied to pharmacokinetic study of the caffeic acid, ferulic acid, formononetin,\ncryptotanshinone, and tanshinone IIA in rats after oral administration of NXTC at single and triple dose....
In this study, we systematically investigated the plasma pharmacokinetics, tissue\ndistribution, and elimination of three active alkaloids after oral administration of the effective\nfraction of alkaloids from Ramulus Mori (SZââ?¬â??A)ââ?¬â?an innovative hypoglycemic agentââ?¬â?in rats.\nMoreover, the influences of other components in SZââ?¬â??A on dynamic process of alkaloids were\nexplored for the first time. The results showed that 1-deoxynojirimycin (DNJ), fagomine (FGM)\nand 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) exhibited nonlinear pharmacokinetics following\noral administration of SZââ?¬â??A (40ââ?¬â??1000 mg/kg). The prolonged t1/2 and greater area under\nconcentration-time curve (AUC) versus time (AUC0ââ?¬â??t) of DNJ for SZââ?¬â??A than for purified DNJ has\nbeen observed after both oral and intravenous administration. It was found that other components\nin SZââ?¬â??A could enhance the absorption of DNJ through the intestinal barrier. The major distribution\ntissues of DNJ, FGM, and DAB were the gastrointestinal tract, liver, and kidney. Three alkaloids were\nmainly excreted into urine and feces, but less into bile. Interestingly, the excess excretion of FGM was\nrevealed to be partly due to the biotransformation of other components in SZââ?¬â??A via gut microbiota.\nThese information provide a rational basis for the use of SZââ?¬â??A in clinical practice....
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