scholarly journals An Approach to Predict the Ductus-Arteriosus Dilating Effect Induced by Lipo-Prostaglandin E1 in Newborn Rats Lacking Plasma Concentration-Time Data by the Pharmacological Response Kinetic Model

2003 ◽  
Vol 26 (2) ◽  
pp. 210-215 ◽  
Author(s):  
Keita Yamauchi ◽  
Shoji Yasunaga ◽  
Hiromu Kawasaki ◽  
Yuji Kurosaki
Keyword(s):  
Plasma Concentration ◽  
Kinetic Model ◽  
Prostaglandin E1 ◽  
Ductus Arteriosus ◽  
Newborn Rats ◽  
Time Data ◽  
Concentration Time ◽  
Pharmacological Response

scholarly journals Vitamin K absorption and kinetics in human subjects after consumption of13C-labelled phylloquinone from kale

2010 ◽  
Vol 104 (6) ◽  
pp. 858-862 ◽  
Author(s):  
Janet A. Novotny ◽  
Anne C. Kurilich ◽  
Steven J. Britz ◽  
David J. Baer ◽  
Beverly A. Clevidence
Keyword(s):  
Plasma Concentration ◽  
Detection Limit ◽  
Vitamin K ◽  
Peak Plasma ◽  
Human Subjects ◽  
Peak Plasma Concentration ◽  
Plasma Samples ◽  
Time Data ◽  
Compartmental Modelling ◽  
Concentration Time

The absorption and plasma disappearance of vitamin K were investigated by uniformly labelling phylloquinone in kale with carbon-13, and by feeding the kale to study subjects. Seven healthy volunteers ingested a single 400 g serving of kale with 30 g vegetable oil. The kale provided 156 nmol of phylloquinone. Serial plasma samples were collected and analysed for the appearance of13C-phylloquinone by HPLC–MS. Six of the subjects showed significant amounts of labelled phylloquinone in plasma, though one subject's plasma was not consistently enriched above the detection limit, and this subject's baseline plasma phylloquinone level was the lowest in the group. After ingestion of the labelled kale, plasma13C-phylloquinone concentration increased rapidly to a peak between 6 and 10 h, and then rapidly decreased. Average peak plasma concentration for the six subjects with detectable13C-phylloquinone was 2·1 nmol/l. Plasma concentration–time data were analysed by compartmental modelling. Modelling results demonstrated a mean (n6) bioavailability of phylloquinone from kale to be 4·7 %. Plasma and tissue half-times for phylloquinone were found to be 8·8 and 215 h, respectively.

scholarly journals Larger Dose Reductions of Vancomycin Required in Neonates with Patent Ductus Arteriosus Receiving Indomethacin versus Ibuprofen

2019 ◽  
Vol 63 (8) ◽  
Author(s):  
S. Cristea ◽  
K. Allegaert ◽  
A. C. Falcao ◽  
F. Falcao ◽  
R. Silva ◽  
...  
Keyword(s):  
Patent Ductus Arteriosus ◽  
Pharmacokinetic Model ◽  
Ductus Arteriosus ◽  
Preterm Neonates ◽  
Population Pharmacokinetic ◽  
Time Data ◽  
Data Set ◽  
Concentration Time ◽  
The Impact ◽  
Patent Ductus

ABSTRACT Ibuprofen and indomethacin are commonly used to induce ductus arteriosus closure in preterm neonates. Our group previously reported that ibuprofen decreased vancomycin clearance by 16%. In this study, we quantified the impact of indomethacin coadministration on vancomycin clearance by extending our vancomycin population pharmacokinetic model with a data set containing vancomycin concentrations measured in preterm neonates comedicated with indomethacin. The modeling data set includes concentration-time data of vancomycin administered alone or in combination with either ibuprofen or indomethacin collected in the neonatal intensive care units of UZ Leuven (Leuven, Belgium) and São Francisco Xavier Hospital (Lisbon, Portugal). The derived vancomycin pharmacokinetic model was subsequently used to propose dose adjustments that yield effective vancomycin exposure (i.e., area under the concentration-time curve from 0 to 24 h [AUC0–24] between 300 to 550 mg·h/liter, with a probability of <0.1 of subtherapeutic exposure) in preterm neonates with patent ductus arteriosus. We found that indomethacin coadministration reduced vancomycin clearance by 55%. Model simulations showed that the most recent vancomycin dosing regimen, which was based on an externally validated model, requires 20% and 60% decreases of the loading and maintenance doses of vancomycin, respectively, when aiming for optimized exposure in the neonatal population. By analyzing vancomycin data from preterm neonates comedicated with indomethacin, we found a substantial decrease in vancomycin clearance of 55% versus a previously reported 16% for ibuprofen. This decrease in clearance impacts vancomycin dosing, and we anticipate that other drugs eliminated by glomerular filtration are likely to be affected to a similar extent as vancomycin.

scholarly journals PHARMACOKINETIC COMPARISON OF MONTELUKAST SODIUM FORMULATIONS AFTER A SINGLE ORAL DOSE IN HEALTHY GUINEA PIGS

2019 ◽  
pp. 165-169
Author(s):  
NEELAM SINGH ◽  
Giriraj T Kulkarni ◽  
Yatendra Kumar ◽  
GIRIRAJ T KULKARNI
Keyword(s):  
Plasma Concentration ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Guinea Pigs ◽  
Elimination Rate ◽  
Pharmacokinetic Parameters ◽  
Time Data ◽  
Concentration Time ◽  
Montelukast Sodium ◽  
Significant Difference

Objective: Pharmacokinetic evaluation of montelukast sodium chronomodulated capsules (sustained-release solid dispersion of drug enclosed in pH-sensitive film-coated hard gelatin shell) and marketed tablets has been carried out in this study. Methods: A single oral dose of prepared capsules and marketed conventional tablets was administered in healthy male Dunkin-Hartley albino guinea pigs. Blood samples were collected at different time intervals and plasma concentration of drug was determined by reversed-phase high-performance liquid chromatography. Different pharmacokinetic parameters were assessed from plasma drug concentration-time profile by one-compartment model, first-order kinetics. Results: Pharmacokinetic parameters such as time to reach maximum concentration, elimination rate constant, elimination half-life, and mean residence time data indicates that drug release from chronomodulated capsules is significantly prolonged with initial release lag time of 3.5–4 h in comparison with marketed conventional tablets. However, maximum drug plasma concentration, area under the concentration-time curve, and apparent volume of distribution values show non-significant difference between capsules and marketed tablets. Conclusion: The findings specified that capsules were providing time controlled delivery of drug at a desired rate for prolonged time, which may be helpful for the prevention of episodic attack of asthma in early morning hours.

Nitrate and chloride formation in chloramination

1994 ◽  
Vol 30 (9) ◽  
pp. 101-110
Author(s):  
V. Diyamandoglu
Keyword(s):  
Kinetic Model ◽  
Analytical Method ◽  
Kinetic Data ◽  
Experimental Results ◽  
Mass Balances ◽  
Time Profiles ◽  
Slow Decay ◽  
Concentration Time ◽  
End Products ◽  
Chlorine Residuals

The formation of nitrate and chloride as end-products of chloramination (combined chlorination) was investigated at pH ranging between 6.9 and 9.6 at 25°C. The experimental results comprised concentration-time profiles of combined chlorine residuals along with nitrate and chloride. Nitrite, if present, was always below the detectibility limit of the analytical method used (25 ppb). Mass balances on chlorine species depicted that chloride formed during the slow decay of combined chlorine residuals does not account for all the chlorine lost. This substantiates the formation of other reaction end-products which are yet to be identified. A kinetic model for chloramination is proposed based on the kinetic data obtained in this study.

scholarly journals Physiologically Based Pharmacokinetic Models of Probenecid and Furosemide to Predict Transporter Mediated Drug-Drug Interactions

2020 ◽  
Vol 37 (12) ◽  
Author(s):  
Hannah Britz ◽  
Nina Hanke ◽  
Mitchell E. Taub ◽  
Ting Wang ◽  
Bhagwat Prasad ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Organic Anion ◽  
Plasma Concentrations ◽  
Whole Body ◽  
Time Profiles ◽  
Pbpk Models ◽  
Physiologically Based Pharmacokinetic ◽  
Concentration Time ◽  
Anion Transporter ◽  
Physiologically Based

Abstract Purpose To provide whole-body physiologically based pharmacokinetic (PBPK) models of the potent clinical organic anion transporter (OAT) inhibitor probenecid and the clinical OAT victim drug furosemide for their application in transporter-based drug-drug interaction (DDI) modeling. Methods PBPK models of probenecid and furosemide were developed in PK-Sim®. Drug-dependent parameters and plasma concentration-time profiles following intravenous and oral probenecid and furosemide administration were gathered from literature and used for model development. For model evaluation, plasma concentration-time profiles, areas under the plasma concentration–time curve (AUC) and peak plasma concentrations (Cmax) were predicted and compared to observed data. In addition, the models were applied to predict the outcome of clinical DDI studies. Results The developed models accurately describe the reported plasma concentrations of 27 clinical probenecid studies and of 42 studies using furosemide. Furthermore, application of these models to predict the probenecid-furosemide and probenecid-rifampicin DDIs demonstrates their good performance, with 6/7 of the predicted DDI AUC ratios and 4/5 of the predicted DDI Cmax ratios within 1.25-fold of the observed values, and all predicted DDI AUC and Cmax ratios within 2.0-fold. Conclusions Whole-body PBPK models of probenecid and furosemide were built and evaluated, providing useful tools to support the investigation of transporter mediated DDIs.

Comparison of the Effect-site keOs of Propofol for Blood Pressure and EEG Bispectral Index in Elderly and Younger Patients

1999 ◽  
Vol 90 (6) ◽  
pp. 1517-1527. ◽  
Author(s):  
Tomiei Kazama ◽  
Kazuyuki Ikeda ◽  
Koji Morita ◽  
Mutsuhito Kikura ◽  
Matsuyuki Doi ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Plasma Concentration ◽  
Bispectral Index ◽  
Time Course ◽  
Drug Infusion ◽  
Time Data ◽  
Aged Patients ◽  
Younger Patients ◽  
Spectral Edge Frequency ◽  
Effect Site

Background Drug effect lags behind the blood concentration. The goal of this investigation was to determine the time course of plasma concentration and the effects of propofol demonstrated by electroencephalogram or blood pressure changes and to compare them between elderly and young or middle-aged patients. Methods A target-controlled infusion was used to rapidly attain and maintain four sequentially increasing, randomly selected plasma propofol concentrations from 1 to 12 microg/ml in 41 patients aged 20-85 yr. The target concentration was maintained for about 30 min. Bispectral index (BIS), spectral edge frequency, and systolic blood pressure (SBP) were used as measures of propofol effect. Because the time courses of these measures following the started drug infusion showed an exponential pattern, the first-order rate constant for equilibration of the effect site with the plasma concentration (k(eO)) was estimated by fitting a monoexponential model to the effect versus time data resulting from the pseudo-steady-state propofol plasma concentration profile. Results The half-times for the plasma-effect-site equilibration for BIS were 2.31, 2.30, 2.29, and 2.37 min in patients aged 20-39, 40-59, 60-69, and 70-85 yr, respectively (n = 10 or 11 each). The half-times for SBP were 5.68, 5.92, 8.87, and 10.22 min in the respective age groups. All were significantly longer than for BIS (P &lt; 0.05). The propofol concentration at half of the maximal decrease of SBP was significantly greater (P &lt; 0.05) in the elderly than in the younger patients. Conclusions The effect of propofol on BIS occurs more rapidly than its effect on SBP. Age has no effect on the rate of BIS reduction with increasing propofol concentration, whereas with increasing age, SBP decreases to a greater degree but more slowly.

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