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Search Results: 1 - 10 of 142 matches for " pharmacokinetic "
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Comparative Pharmacokinetic Study between Metformin Alone and Combined with Orlistat in Healthy Mexican Volunteers  [PDF]
Noemí Santos-Caballero, Francisco Javier Flores-Murrieta
Pharmacology & Pharmacy (PP) , 2012, DOI: 10.4236/pp.2012.33040
Abstract: Traditional treatment of type 2 diabetes mellitus (T2DM) has focused on correcting hyperglycemia. However, T2DM is almost always accompanied by other conditions and risk factors that affect its morbidity and mortality. Obesity represents one of the main risk factors associated in the T2DM and a modest weight loss around 5% is linked with significant reduction in the blood glucose levels. The objective of this study was to compare the pharmacokinetic parameters between two formulations of metformin, alone or combined with orlistat, in healthy volunteers. A single-blinded, single dose, two-period, two-sequence, crossover, randomized and balanced study design with a 7-day washout period was performed in 26 Mexican volunteers. Plasma samples were collected over a 24-hour period after administration of 500 mg metformin alone or combined with 60 mg orlistat in each period. A validated high-performance liquid chromatography coupled with a ultraviolet detector was used to analyze metformin concentration in plasma. Bioequivalence between metformin alone and metformin combined with orlistat was determined when the ratio for the 90% confidence intervals (CI) of area under the curve (AUC24h) and maximum concentration (Cmax) of the two formulations were within 80% and 125%. In the current study, the mean ± standard deviation (SD) of Cmax, AUC24h and AUC of the formulation containing only metformin were 1.39 ± 0.44 μg/mL, 7.59 ± 3.17 μg h/mL and 8.48 ± 4.13 μg h/mL, respectively, while the mean ± SD of Cmax, AUC24h and AUC of the formulation containing metformin and orlistat were 1.38 ± 0.48 μg/mL, 7.80 ± 2.83 μg h/mL and 9.13 ± 4.29 μg h/mL, respectively. The parametric 90% CI for Cmax and AUC24h were 87.5-109.3 and 88.7-124.7, respectively. These results suggest that both formulations are bioequivalent and there is not pharmacokinetic interaction between metformin and orlistat.
Pharmacokinetic Prediction of Levofloxacin Accumulation in Tissue and Its Association to Tendinopathy  [PDF]
Loan Pham, John M. Christensen, Rosita Rodriguez-Proteau
Pharmacology & Pharmacy (PP) , 2013, DOI: 10.4236/pp.2013.41018
Abstract: Objectives: We investigated pharmacokinetic tissue distributions of Levofloxacin to explain adverse tendon incidents. Methods: The pharmacokinetic profiles of single and multiple dosing of 500 mg Levofloxacin following oral and IV infusion administration were simulated. Monte Carlo simulation was used to simulate the drug concentration profiles in plasma and tissue after seven dosing regimens while varying the drug’s elimination and distribution rates to analyze the effects of changing those rates on Levofloxacin accumulation in tissue. Results: Simulated data following oral and IV administration reflect well the reported data (mean simulated plasma Cmax = 6.59 μg/mL and 5.19 μg/mL for IV and oral versus 6.4 μg/mL and 5.2 μg/mL for observed clinical IV and oral route, respectively). Simulations of seven repetitive doses are also in agreement with reported values. Low elimination rates affect the drug concentration in plasma and tissue significantly with the concentration in plasma rising to 35 μg/mL at day 7. Normal elimination rates together with escalation of distribution rates from plasma to tissue increase tissue concentration after 7 doses to 9.5 μg/mL, a value is more than twice that of normal. Conclusions: Simulation can be used to evaluate drug concentration in different tissues. The unexpectedly high concentrations in some cases may explain the reason for tendinopathy in clinical settings.
An LC-MS/MS Method for Determination of Imperatorin and Isoimperatorin in Rat Plasma and Application to a Pharmacokinetic Study  [PDF]
Junbo Xing, Hong Cao, Yumin Chen, Caihong Shui, Tingting Shan, Dan Hu
Pharmacology & Pharmacy (PP) , 2013, DOI: 10.4236/pp.2013.45059
Abstract: A highly sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed for the de-termination of imperatorin and isoimperatorin in rat plasma using psoralen as internal standard. Analyses were performed on a Shimadzu HPLC system using a Shimadzu C18 column eluted with a mobile phase of methanol-water (25:75), containing 0.1% formic acid at a flow rate of 0.4 ml/min. The detection was performed by positive ion elec-trospray ionization in multiple reactions monitoring mode, monitoring the transitions m/z 203→147 and m/z 203→159 for imperatorin and isoimperatorin, respectively. The method was validated over the concentration range of 2.5 -1000.0 ng/mL for imperatorin and isoimperatorin. The limits of detection and quantification were 1.0 and 3.0 ng/mL, repectively for both analytes. The intra-day and inter-day accuracy and precision of the assay were less than 10.9%. This method has been applied successfully to a pharmacokinetic study involving the intragastric administration of extract of Angelicae Dahuricae Radix to rats.
Determination of Candesartan and Hydrochlorothiazide in Human Plasma by HPLC Coupled with Mass Spectrometry  [PDF]
Olga S. Brushinina, Roman V. Gurto, Maksim S. Timofeev, Galina A. Frelikh, Vladimir A. Slepichev, Elena A. Yanovskaya, Natalia U. Polomeeva, Yulya G. Zyuz’kova, Vladimir V. Udut
International Journal of Analytical Mass Spectrometry and Chromatography (IJAMSC) , 2014, DOI: 10.4236/ijamsc.2014.22003
Abstract:

Quantitative determination of hydrochlorothiazide (HCTZ) and candesartan (CDS) in human plasma in volunteers was performed using a sensitive, selective and specific LC-MS method which has been developed and validated before the study. The study was performed by means of a liquid chromatograph Shimadzu Prominence equipped with a mass spectrometer LCMS-2020. Analytical column PerfectBond ODS-HD HPLC-column 5 μm 250 × 3.0 mm with a pre-column cartridge PerfectBond ODS-HD 5 μm 10 × 3.0 mm, double source of ionization for LCMS-2020 (electrospray (ESI) and chemical (APCI)) and software LabSol LCMS V5 LCMS2020 systempack were used. The low limit of the quantitative determination for HCTZ and CDS made up 10 ng/ml. m/z for CDS 441.20—positive scan, m/z for HCTZ 295.90—negative scan. The method has been applied to a pharmacokinetic study of 12.5 mg HCTZ and 16 mg CDS tablet in healthy volunteers.

Oral Pharmacokinetics of Mirodenafil in Mexican Healthy Volunteers  [PDF]
Miriam del Carmen Carrasco-Portugal, Francisco Javier Flores-Murrieta, Juan Gerardo Reyes-García, Noemí Santos-Caballero
Pharmacology & Pharmacy (PP) , 2014, DOI: 10.4236/pp.2014.51016
Abstract:

Mirodenafil is a 5-phosphodiesterase inhibitor that is currently marketed in Korea for the treatment of erectile dysfunction; however, no information in other populations is available. It has been described that Mirodenafil is metabolized by CYP3A4, a metabolic pathway in which interethnic differences have been reported. The purpose of this study was to characterize the oral pharmacokinetics of Mirodenafil in Mexicans. Seventeen male healthy volunteers were enrolled in this study. After an overnight fast, volunteers received an oral 100 mg dose and blood samples were collected at selected times during 24 h. Plasma was stored frozen and analyzed by an HPLC method. Pharmacokinetic parameters obtained were: Cmax 331.129 ± 32.689 ng/mL, tmax 1.574 ± 0.293 h, AUC24h 883.293 ± 104.088 ng·h/mL, AUC 976.477 ± 108.812 ng·h/mL and t1/2 1.807 ± 0.171 h. Parameter values observed in this study are similar to those reported in Koreans. Since efficacy and safety studies of Mirodenafil have been conducted in Koreans, it is expected that dosage regime to employ in Mexicans should be similar to the approved for Korean population.

Farmacocinética plasmática de la balofloxacina en terneros
García Ovando,Hugo; Prieto,Guillermo F; Lüders,Carlos F; Errecalde,Carlos A;
Revista Colombiana de Ciencias Pecuarias , 2008,
Abstract: pharmacokinetic parameters of absorption and disposition of balofloxacin were determined in female holando-argentinean calves (n = 6), after a 5 mg/kg single dose, administered as both intravenous and subcutaneous bolus, in a crossed-over design treatment. the analyte was determined in plasma samples by microbiological method in agar diffusion, using a bacillus subtilis bga spore solution as microorganism detector in agar antibiotic no 1. the plasmatic concentrations of balofloxacin based on the time were analyzed by a non compartimental kinetic model using software pk solution 2.0. the intravenous pharmacokinetic parameters obtained were: t1/2β= 2.3 ± 1.1 h; cltotal area= 10.2 ± 3.4 ml/min/kg; vdárea= 1.8 ± 0.3 l/kg; and aucárea= 551.3 ± 247.0 μg/min/ml. except for cltotal area and aucarea, the values obtained for the intravenous administration significantly differed from the obtained ones for the subcutaneous route (p<0.05), for which cmax= 1.3 ± 0.4 μg/ml, tmax= 51 ± 12.1 minutes and bioavailability values close to 98% were obtained. the vdarea value was superior to 1 l/kg for both routes of application and indicates good capacity to spread to extravascular area and tissues.
Principios farmacocinéticos y farmacodinámicos en el tratamiento de ni?os con otitis media
Aguilar-Morales,Lara; Soley-Gutiérrez,Carolina; Arguedas-Mohs,Adriano;
Acta Médica Costarricense , 2006,
Abstract: because acute respiratory infections and particularly acute otitis media (aom), are the most common cause of antimicrobial prescription in pediatric patients, it is important to optimize antimicrobial therapies. it is essential that before prescribing an antimicrobial agent, the aom diagnosis is well established and the local microbiological pattern is known. the present review incorporates novel concepts for the selection of the antimicrobial therapy in children with aom taking into account pharmacokinetic and pharmacodynamic principles applied to microbiologycal concepts. these new concepts have revolutionized the treatment of diverse infectious diseases in pediatric patients and particularly in the treatment of children with otitis media.
Monitoreo terapéutico de vancomicina en una terapia intensiva pediátrica
Zylbersztajn,Brenda L; Travaglianti,Mónica; Weller,Gregorio; Mato,Horacio G;
Archivos argentinos de pediatr?-a , 2008,
Abstract: introduction. vancomycin is used in pediatric patients usually at 40 mg/kg/day four times daily. recent data demonstrated the need of large doses to reach therapeutic concentrations in critical patients. objective. describe dosage regime of vancomycin in patients from a pediatric intensive care unit, register values of plasmatic concentrations and determine the regimes necessary to reach therapeutic troughs. population, materials and methods. we made an observational, retrospective study. patients who received vancomycin by more than two days where studied. patients who didn't register vancomycin troughs (minimum values) and/or with elevated serum creatinine were excluded. the age, grouping in younger than (<) 2 years and older than (>) 2 years and troughs of vancomycin were registered. volume of distribution (vd) and half-life (t 1/2) were obtained. results. we studied 97 patients. patients with undetectable plasmatic concentrations younger than two years were 14 and the older ones were 9, this difference was not statistically significant (p= 0.063). mediam of the regime of administration for the younger group was 50 mg/kg/day each 6 h and for the older 40 mg/kg/day four times a day. mediam (range) of vd and half-life (t 1/2) for the group of < 2 years and >2 years were 0.682 (0.504-1.06) l/kg, 6.12 (2.66-17.49) h; 0.685 (0.389-1.198) l/kg, 4.88 (3.59-15.4) h, without significant differences. conclusions. dosage regime required an increase in frequency, in addition there were no significant differences between pharmacokinetic parameters and final administration regime for both groups, being able to suppose that equal schemes of administration could be implemented more frequently.
Estudio farmacocinético de amiodarona en perros
SAAVEDRA,I.; MANRíQUEZ,C.; GAETE,L.; MANTEROLA,L.; SAAVEDRA,M.; PINEDA,M.;
Archivos de medicina veterinaria , 1999, DOI: 10.4067/S0301-732X1999000200015
Abstract: pharmacokinetic variables of amiodarone were studied in six healthy dogs. plasma levels of amiodarone and its metabolite, desethylamiodarone, were determinated by hplc at different moments, after an i.v. administration as infusion of 5 mg/kg in two minutes. a compartment model independent pharmacokinetic analysis program was used to evaluate plasma levels of amiodarone vs time. the following results were obtained: auc: 9.95 ± 2.91 mg/ml/hr, b: 0.25 ± 0.27 l/hr, cl: 8.82 ± 1.95 ml/min./kg, tmr: 7.38 ± 1.52 hrs, t1/2b 5.056 ± 4.5 hrs and vd: 3.424 ± 2.3 l/kg. amiodarone pharmacokinetic disposition presented a rapid distribution and decrease from blood during the first 30 minutes after i.v. then it was slowly eliminated. it is concluded that amiodarone is an alternative to be considered in cardiac pathology in dogs, since the pharmacokinetic parameters, similar to those of human volunteers, can contribute to determine the apropiate dose to be administered
Farmacocinética de propofol en potrillos de 10 a 15 días de edad
BARONI,E.; AHUMADA,F.; LüDERS,C.; SAAVEDRA,I.; ZAMBUCETTI,R.;
Archivos de medicina veterinaria , 2000, DOI: 10.4067/S0301-732X2000000200006
Abstract: pharmacokinetic variables of propofol were studied in 8 foals. plasma levels of propofol at different time after a single intravenous dose of 2.4 mg/kg bw, were determined by hplc. an open two compartments model was used to evaluate plasma levels of propofol and values of t1/2a, t1/2b, vdc, vdss, vdb, cltotal y mrt were obtained. propofol pharmacokinetic disposition showed a rapid distribution and removal from organic tissues, and the reported pharmacokinetic variables contribute to determine the appropriate dose to be given
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