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Total Plasma Concentration (total + plasma_concentration)
Selected AbstractsEffects of altered plasma ,-1-acid glycoprotein levels on pharmacokinetics of some basic antibiotics in pigs: simulation analysisJOURNAL OF VETERINARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2001M. Kuroha Effects of altered plasma , -1-acid glycoprotein (AGP) levels on pharmacokinetic parameters of basic antimicrobials, erythromycin (EM), lincomycin (LM) and clindamycin (CM) were evaluated in pigs by simulation analysis. Intravenous (i.v.) injections of EM, LM and CM were performed to obtain pharmacokinetic parameters in healthy conditions. Binding parameters were obtained from an in vitro study using ultrafiltration. Simulation studies indicated that an increase of plasma AGP levels resulted in a decrease of both volume of distribution at steady state (Vdss) and total body clearance (Cltot) for all the drugs. Elimination rate constant for LM was almost unchanged by an increase of plasma AGP levels, whereas those for EM and CM were increased. Plasma concentration,time profiles at a high AGP level (often observed in pathophysiological conditions) were also simulated. All of the total plasma concentration,time profiles were different from those at normal AGP level. The differences were characterized by a higher initial concentration with faster or similar elimination. Unbound plasma concentration,time profile of LM was unaffected by AGP levels, whereas EM and CM were eliminated from plasma more rapidly at high AGP level. These results suggested that adjustment of dosage regimen of EM and CM is required in pathophysiological conditions, but that of LM is not required. [source] Determination of acyclovir in horse plasma and body fluids by high-performance liquid chromatography combined with fluorescence detection and heated electrospray ionization tandem mass spectrometryBIOMEDICAL CHROMATOGRAPHY, Issue 2 2009A. Maes Abstract Two methods are presented for the determination of ,respectively' the plasma protein unbound and total concentration of acyclovir in horse plasma and body fluids: first, a liquid,liquid extraction was performed on plasma, combined with HPLC-fluorescence detection for the total plasma concentration; second a more sensitive method using high-performance liquid chromatography combined with heated electrospray ionization tandem mass spectrometry (LC-HESI-MS/MS) was described for plasma and for body fluids analysis. To obtain the unbound concentration of acyclovir in plasma, a simple deproteinization step using a Microcon® filter was performed. Ganciclovir was used as an internal standard. Analysis was carried out on an Inertsil 5 ODS-3 column for the HPLC-fluorescence method. For the LC-HESI-MS/MS method a PLRP-S column was used. The limit of quantification (LOQ) for the total concentration was set at 50 and 2 ng mL,1 for the HPLC-fluorescence method and the LC-HESI-MS/MS method, respectively. The limit of quantification for the unbound concentration was set at 5 ng mL,1 and at 2 ng mL,1 for body fluids. The methods were successfully used to perform pharmacokinetic and clinical studies in horses after intravenous and oral dosage of acyclovir and its prodrug valacyclovir. Copyright © 2008 John Wiley & Sons, Ltd. [source] Pharmacokinetics of CPX-351 (cytarabine/daunorubicin HCl) liposome injection in the mouseJOURNAL OF PHARMACEUTICAL SCIENCES, Issue 7 2009William F. Bayne Abstract CPX-351 (cytarabine/daunorubicin liposome injection) is a liposomal formulation of a synergistic, fixed combination of the antineoplastic drugs cytarabine and daunorubicin for intravenous infusion. The two drugs are contained within the liposome in a 5:1 molar ratio, shown to be synergistic in vitro and in murine models of hematological malignancies. Mice were given a single intravenous dose of CPX-351 or conventional cytarabine and daunorubicin in saline and plasma and bone marrow were assayed for drug and lipid concentrations. A pharmacokinetic model was developed to assess the disposition of the coencapsulated drugs in mice, including the free and encapsulated fractions after measurement of the total plasma concentrations. Through the measurement of the loss of both encapsulated drug and liposomal lipid from the plasma, the routes of elimination, extravasation (uptake of encapsulated drugs into the tissues) and leak (passage of the drugs across the liposome membrane into the plasma), could be discerned. Knowing the leak rates from the liposome into the plasma and the plasma pharmacokinetics of the conventional drugs, the free drug concentrations could be predicted. The free concentrations in the bone marrow from the liposome leak in plasma could also be predicted using the bone marrow responses to the conventional drugs. © 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2540,2548, 2009 [source] Elevated plasma fibrinogen ,, concentration is associated with myocardial infarction: effects of variation in fibrinogen genes and environmental factorsJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2007M. N. MANNILA Summary., Background:, Fibrinogen ,,, a fibrinogen ,-chain variant generated via alternative mRNA processing, has been associated with susceptibility to thrombotic disease. Objective:, The present case,control study searched for potential determinants of the plasma fibrinogen ,, concentration and examined the relationship between this variant and risk of myocardial infarction (MI). Patients and methods:, The Stockholm Coronary Artery Risk Factor study, comprising 387 postinfarction patients and 387 healthy individuals, was employed. The fibrinogen gamma (FGG) 9340T > C [rs1049636], fibrinogen alpha (FGA) 2224G > A [rs2070011] and fibrinogen beta (FGB) 1038G > A [rs1800791] polymorphisms were determined. The plasma fibrinogen ,, concentration was measured by enzyme-linked immunosorbent assay. The multifactor dimensionality reduction method was used for interaction analyses on risk of MI. Results:, The FGG 9340T > C and FGA 2224G > A polymorphisms, total plasma concentrations of fibrinogen, insulin and high-density lipoprotein, and gender appeared to be independent determinants of plasma fibrinogen ,, concentration in patients, and the corresponding determinants in controls included FGG 9340T > C and FGA 2224G > A polymorphisms and plasma fibrinogen concentration. An elevated plasma fibrinogen ,, concentration proved to be an independent predictor of MI [adjusted odds ratio (OR) (95% CI): 1.24 (1.01, 1.52)]. The plasma fibrinogen ,, concentration was involved in a high-order interaction with total plasma fibrinogen and the FGG 9340T > C and FGA 2224G > A polymorphisms, associated with a further increased risk of MI [OR (95% CI): 3.22 (2.35, 4.39)]. Conclusions:, Plasma fibrinogen ,, concentration influences the risk of MI, and this relationship seems to be strengthened by the presence of an elevated total plasma fibrinogen concentration and the FGG 9340T and FGA 2224G alleles. [source] | |||||||||||||