Efflux du 36Cl et distribution du Cl dans le muscle papillaire du lapin, effet de l'ouabaïne

1981 ◽  
Vol 59 (8) ◽  
pp. 794-799
Author(s):  
Jean-Pierre Caillé
Keyword(s):  
Rate Constant ◽  
Papillary Muscle ◽  
Compartment Model ◽  
Rapid Rate ◽  
Extracellular Medium ◽  
Cellular Compartment ◽  
Rapid Exchange ◽  
Two Compartment Model ◽  
In Series

The 36Cl efflux "in vivo" was measured in the rabbit papillary muscle to determine the Cl distribution in the muscle and to evaluate the effect of ouabain on this parameter. The results obtained for the 36Cl efflux are analyzed using either a two-compartment model or a model including diffusion in the extracellular space in series with one compartment. The Cl exchange with 36Cl, *[Cl]i (intracellular Cl content which has participated in exchanges. [Formula: see text]) is computed from the exponential terms of the models. A time exposure of 40 and 80 min to the 36Cl-containing solution led to the same exchange Cl content: 20.5 and 23.9 mmol/kg cells. Addition of ouabain (10−6M) slightly increased the rate constant of the cellular compartment, but did not influence the *[Cl]i. In the presence of ouabain (10−6M), there was a significant increase in the efflux component with a rapid rate constant. These results can be interpreted as follows: the Cl intracellular concentration is not affected by ouabain; thus, the increase in total Cl content induced in the papillary muscle by ouabain is located in a compartment having a very rapid exchange velocity with the extracellular medium.[Journal translation]

Rapid changes in hepatic glucose output after a pulse of growth hormone in dogs

1984 ◽  
Vol 246 (1) ◽  
pp. E14-E20
Author(s):  
P. Vaitkus ◽  
A. Sirek ◽  
K. H. Norwich ◽  
O. V. Sirek ◽  
R. H. Unger ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Venous Blood ◽  
Compartment Model ◽  
Glucose Turnover ◽  
Base Line ◽  
Indwelling Catheter ◽  
Two Compartment Model ◽  
Portal Venous Blood ◽  
Glucose Output

In response to a single intravenous injection of bovine growth hormone (GH, 100 micrograms/kg) the non-steady-state turnover of glucose, as well as portal levels of insulin (IRI), glucagon (IRG), somatostatin (SRIF), and glucose were determined in normal conscious dogs. Using the two-compartment model validated to calculate rapid turnover changes and tracer infusion methods, the rate of hepatic output of glucose [Ra(t)] was found to be increased, reaching a maximum of 224 mg/min, 7.4 times the basal rate, 4 min after injection of GH. Ra(t) returned to its basal level 35 min later in a damped oscillatory manner. Hormone determinations were carried out in portal venous blood drawn every 2 min for 2 h from an indwelling catheter. IRG peaked 2 min after GH injection and levels of IRI, SRIF, and glucose peaked between 4 and 8 min. Hormone concentrations returned to normal, i.e., were oscillating around base-line levels, about 30 min after GH. These experiments demonstrate for the first time in vivo that a pulse of GH causes transient changes of glucose turnover and measurable alterations of the hormonal homeostasis in the splanchnic area.

scholarly journals 1573. Population Pharmacokinetic Analyses for Cefepime in Adult and Pediatric Patients

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S574-S575
Author(s):  
Jiajun Liu ◽  
Michael Neely ◽  
Jeffrey Lipman ◽  
Fekade B Sime ◽  
Jason Roberts ◽  
...  
Keyword(s):  
Rate Constant ◽  
Pediatric Patients ◽  
Validation Cohort ◽  
External Validation ◽  
Compartment Model ◽  
Volume Of Distribution ◽  
Information Criteria ◽  
Population Pharmacokinetic ◽  
Final Model ◽  
Two Compartment Model

Abstract Background Cefepime (CEF) is commonly used for adult and pediatric infections. Several studies have examined CEF’s pharmacokinetics (PK) in various populations; however, a unifying PK model for adult and pediatric subjects does not yet exist. We developed a combined population model for adult and pediatric patients and validated the model. Methods The initial model includes adult and pediatric patients with a rich cefepime sampling design. All adults received 2 g CEF while pediatric subjects received a mean of 49 (SD 5) mg/kg. One- and two-compartment models were considered as base models and were fit using a non-parametric adaptive grid algorithm within the Pmetrics package 1.5.2 (Los Angeles, CA) for R 3.5.1. Compartmental model selection was based on Akaike information criteria (AIC). Covariate relationships with PK parameters were visually inspected and mathematically assessed. Predictive performance was evaluated using bias and imprecision of the population and individual prediction models. External validation was conducted using a separate adult cohort. Results A total of 45 subjects (n = 9 adults; n = 36 pediatrics) were included in the initial PK model build and 12 subjects in the external validation cohort. Overall, the data were best described using a two-compartment model with volume of distribution (V) normalized to total body weight (TBW/70 kg) and an allometric scaled elimination rate constant (Ke) for pediatric subjects (AIC = 4,138.36). Final model observed vs. predicted plots demonstrated good fit (population R2 = 0.87, individual R2 = 0.97, Figure 1a and b). For the final model, the population median parameter values (95% credibility interval) were V0 (total volume of distribution), 11.7 L (10.2–14.6); Ke for adult, 0.66 hour−1 (0.38–0.78), Ke for pediatrics, 0.82 hour−1 (0.64–0.85), KCP (rate constant from central to peripheral compartment), 1.4 hour−1 (1.3–1.8), KPC (rate constant from peripheral to central compartment), 1.6 hour−1 (1.2–1.8). The validation cohort has 12 subjects, and the final model fit the data well (individual R2 = 0.75). Conclusion In this diverse group of adult and pediatrics, a two-compartment model described CEF PK well and was externally validated with a unique cohort. This model can serve as a population prior for real-time PK software algorithms. Disclosures All authors: No reported disclosures.

BIOSYNTHESIS OF C19 STEROIDS FROM 4-14C-CHOLESTEROL AND 7-3H-PREGNENOLONE IN VIVO: CONSIDERATION OF NEW PATHWAYS

1962 ◽  
Vol 40 (2) ◽  
pp. 188-202 ◽  
Author(s):  
Shlomo Burstein ◽  
Ralph I. Dorfman
Keyword(s):  
Adrenal Adenoma ◽  
Mevalonic Acid ◽  
Compartment Model ◽  
Side Chain ◽  
Partition Chromatography ◽  
Steroid Nucleus ◽  
Single Intravenous Injection ◽  
Two Compartment Model ◽  
Specific Activities

ABSTRACT 3H and 14C specific activities of dehydroepiandrosterone, androsterone, 3α-hydroxy-5β-androstan-17-one and 3α-hydroxy-5α-androst-16-ene (without dilution) have been determined following a single intravenous injection of 4-14C-cholesterol and 7α-3H-pregnenolone to a virilized woman with an adrenal adenoma and massive dehydroepiandrosterone excretion. Assuming a one compartment model, or a two compartment model in which the injected radioactivity enters the compartment in which the precursor is secreted exclusively, a new pathway by which dehydroepiandrosterone is formed from cholesterol not through pregnenolone and possibly by cleavage of the side chain C-17 and C-20 is indicated. Analysis of the data by a model in which pregnenolone is secreted into two separate compartments in which progesterone and dehydroepiandrosterone are made, respectively, would explain the findings without necessitating the assumption of a new pathway. 3α-Hydroxy-5α-androst-16-ene was isolated from urine following incubation with β-glucuronidase and partition chromatography on celite suggesting that this steroid is a genuine natural product as surmised by Prelog & Ruzicka (1944) and Brooksbank & Haslewood (1950). 2-14C-Mevalonate was shown to give rise to C19 steroids which is the first in vivo demonstration that mevalonic acid is a precursor of the steroid nucleus in man.

Determination of digesta fill and passage rate from nonabsorbed particulate phase markers using the single dosing method

1989 ◽  
Vol 67 (2) ◽  
pp. 488-494 ◽  
Author(s):  
D. F. Holleman ◽  
R. G. White
Keyword(s):  
Compartment Model ◽  
Time Dependent ◽  
Passage Rate ◽  
Fecal Output ◽  
Two Compartment Model ◽  
Significant Difference ◽  
Single Marker ◽  
Dependent Model ◽  
Digesta Passage

A method is given for analyzing particulate digestive marker data in terms of digesta fill, fecal output, and digesta passage times. The method applies the Stewart – Hamilton Principle to data obtained from a single marker dosing followed by feces sampling; it assumes steady-state conditions for the digesta, but makes no assumptions concerning compartmentalization of digesta. Data analyses are presented for an experiment with sheep in which a particle phase marker, cerium-141 chloride, was used. The estimate of fecal output obtained was 1.8 ± 2.2% (mean percent difference ± SE) greater than the actual fecal output; the in vivo estimate of total digesta fill was 3.3 ± 3.4% less than measured digesta fill. For comparison, the present data were also analyzed using two established compartment modeling approaches, namely a time-independent and a time-dependent two-compartment model. The only significant difference between the estimated parameters as obtained from the Stewart – Hamilton method and the compartmental models was a significantly shorter transit time as estimated by the time-dependent model.

Single Dose Administration of rFVIIa and NN1731 in Two Hemophilia A Dogs.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3144-3144 ◽  
Author(s):  
Mirella Ezban ◽  
Lone Frost ◽  
Dorthe Viuff ◽  
Judi Møss ◽  
Mark Kloos ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Ex Vivo ◽  
Compartment Model ◽  
Initial Distribution ◽  
Coagulation Assays ◽  
Two Compartment Model ◽  
Dose Study ◽  
Related Proteins

Abstract Introduction: The objective of this pilot study was to evaluate and compare the pharmacokinetic and pharmacodynamic (PK/PD) profile of rFVIIa and NN1731 in two hemophilia A dogs. In addition, it was the aim to evaluate the use of TEG for monitoring rFVIIa/NN1731 activity after in vivo administration and to compare with ex vivo spiking data from a previous study. NN1731 is a new rFVIIa analoge with enhanced activity (Allen et al. Arterioscler. Thromb. Vasc. Biol.2007;27:683–689). In hemophilia patients as well as hemophilia dogs the clot formation is impaired and reflected in coagulation assays such as thromboelastography (TEG) and APTT. The choice of hemophilia dogs is based upon the knowledge that the pharmacokinetics of human coagulations factors (FVIII, FIX and rFVIIa) as well as the effective dose is similar to that in humans. In normal dogs, it is not possible to evaluate the effect of these procoagulant proteins in coagulation assays as no impaired clotting is observed. Methods: rFVIIa and NN1731 (280 μg/kg IV) were administered to two hemophilia dogs on separate days and plasma samples collected at different time points. FVIIa activity was measured by the FVIIa clot assay and values were used for pharmacokinetic assessment. The same pharmacokinetic models, a non-compartmental method and a two compartment model, respectively, were used as was the case in the First Human Dosing (FHD) trial of NN1731 (NN1731–1639). Analysis of PD markers in dogs included: APTT, PT and whole blood thromboelastography analysis, recently developed for use in hemophilia dogs. Results: Based on the FVIIa activity profile in the two dogs it was observed that the values obtained at the first time point (C5 min), were higher after treatment with NN1731 than after rFVIIa. All activity based assays including TEG demonstrated that NN1731 was cleared faster than rFVIIa., FVIIa activity (FVIIa clot assay), showed a rapid initial distribution and/or elimination of FVIIa activity (t1/2α:0.3 h) followed by a less rapid elimination phase (t½β:3.5 h). Similar profile and values were obtained for NN1731 in the FHD dose study (J. Møss et al, ISTH, 2007) Conclusions: This study indicates that in hemophilia A dogs, NN1731 and rFVIIa have distinct PK profiles and very similar to what is observed in man. All activity assays show the same qualitative profile, the FVIIa clot assay being the most sensitive assay. The TEG data obtained in vivo are in accordance with the values obtained after in vitro spiking. The data support the use of hemophilia dogs for evaluating the pharmacokinetic and pharmacodynamic profiles of FVIIa related proteins.

A Physiologically Based, Recirculatory Model of the Kinetics and Dynamics of Propofol in Man

2005 ◽  
Vol 103 (2) ◽  
pp. 344-352 ◽  
Author(s):  
Richard N. Upton ◽  
Guy Ludbrook
Keyword(s):  
Management Strategies ◽  
Compartment Model ◽  
The Body ◽  
Data Sets ◽  
Blood Flows ◽  
Two Compartment Model ◽  
Physiologically Based ◽  
Kinetics And Dynamics ◽  
In Series ◽  
Recirculatory Model

Background The disposition of propofol in man is commonly described using a three-compartment mamillary model. However, these models do not incorporate blood flows as parameters. This complicates the representation of the changes in blood flows that may occur in surgical patients. In contrast, complex physiologically based models are derived from data sets (e.g., tissue:blood partition coefficients) that may not be readily collected in man. Methods Alternatively, the authors report a recirculatory model of propofol disposition in a "standard" man that incorporates detailed descriptions of the lungs and brain, but with a lumped description of the remainder of the body. The model was parameterized from data in the literature using a "meta-modeling" approach. The first-pass passage of propofol through the venous vasculature and the lungs was a function of the injected drug mixing with cardiac output and passing through a three-"tank in series" model for the lungs. The brain was represented as a two-compartment model defined by cerebral blood flow and a permeability term. The Bispectral Index was a linear function of the mean brain concentration. The remainder of the body was represented by compartment systems for the liver, fast distribution and slow distribution. Results The model was a good fit of the data and was able to predict other data not used in the development of the model. Conclusions The model may ultimately find a role in improving the fidelity of patient simulators currently used to train anesthetists and for clinical practice simulation to optimize dosing and management strategies.

Transport of radioiodide between thyroid gland and blood in mice and rats

1958 ◽  
Vol 196 (1) ◽  
pp. 113-120 ◽  
Author(s):  
Seymour H. Wollman ◽  
Franklin E. Reed
Keyword(s):  
Single Dose ◽  
Thyroid Gland ◽  
Rate Constant ◽  
Experimental Error ◽  
Compartment Model ◽  
Exit Rate ◽  
Follicular Cells ◽  
Thyroid Activity ◽  
Two Compartment Model ◽  
Rats And Mice

Equilibration data were obtained for thyroids of various activities in rats and mice given a single dose of propylthiouracil to block organic binding of radioiodine. Data were compared with an open two-compartment model of the thyroid characterized by a one-way thyroid clearance of serum radioiodide and an exit rate constant for the transport of radioiodide from the thyroid to the blood. The model generally fitted the data within experimental error. Clearances increased with thyroid activity. Exit rate constants were much larger for animals fed thiouracil than for other animals. Thiocyanate increased the exit rate constant but did not change the thyroid clearance of serum radioiodide significantly. A new open three-compartment thyroid model was introduced and was used to explain how thiocyanate could increase the exit rate constant by inhibiting the transport of iodide from the follicular cells to the lumen of the follicle.

scholarly journals Differentiation of Radioligand Delivery and Binding in the Brain: Validation of a Two-Compartment Model for [11C]Flumazenil

1991 ◽  
Vol 11 (5) ◽  
pp. 745-752 ◽  
Author(s):  
Vjera A. Holthoff ◽  
Robert A. Koeppe ◽  
Kirk A. Frey ◽  
Avram H. Paradise ◽  
David E. Kuhl
Keyword(s):  
Benzodiazepine Receptor ◽  
Occipital Cortex ◽  
Compartment Model ◽  
Stable Measure ◽  
Intravenous Injections ◽  
Audiovisual Stimulation ◽  
Positron Emission ◽  
Two Compartment Model ◽  
Tracer Kinetic

We recently developed a two-compartment, two-parameter tracer kinetic model to estimate the in vivo ligand transport rate ( K1) and distribution volume (DV) for the benzodiazepine antagonist [11C]flumazenil (FMZ) as measured by positron emission tomography (PET). The aim of the present study was to validate that this simplified model provides a stable measure of regional benzodiazepine receptor availability even when ligand delivery is altered. Six young normal volunteers underwent two PET studies subsequent to intravenous injections of [11C]FMZ. Each FMZ study was immediately preceded by measurements of CBF following injection of [15O]water. One set of scans (water/FMZ) was acquired under resting conditions and the other set during audiovisual stimulation. Six additional volunteers underwent two FMZ studies under identical resting conditions. Parametric images were analyzed and a comparison of test-retest studies in the stimulation group revealed a significant increase of CBF and K1 of FMZ in the occipital cortex evoked by visual activation, whereas no regional changes were noted for the DV of FMZ. No significant changes were noted for either K1 or DV of FMZ when comparing studies in the rest-rest setting. The results indicate that the use of a simple two-compartment model for the tracer kinetic analysis of [11C]FMZ makes it possible to separate high-affinity binding from altered radioligand delivery to the human brain.

scholarly journals Decomposition of High-Frequency Electrical Conductivity into Extracellular and Intracellular Compartments based on Two-Compartment Model using Low-to-High Multi-b Diffusion MRI

2020 ◽  
Author(s):  
Mun Bae Lee ◽  
Hyung Joong Kim ◽  
Oh-In Kwon
Keyword(s):  
Electrical Conductivity ◽  
Electrical Properties ◽  
High Frequency ◽  
Compartment Model ◽  
Biological Tissues ◽  
Extracellular Medium ◽  
Two Compartment Model ◽  
Random Decision Forests ◽  
Human Experiments ◽  
Micro Structures

Abstract Background: As an object's electrical passive property, the electrical conductivity is proportional to the mobility and concentration of charged carriers that reflect the brain micro-structures. The measured Mb-DWI data by controlling the degree of applied diffusion weights can quantify the apparent mobility of water molecules within biological tissues. Without any external electrical stimulation, magnetic resonance electrical properties tomography (MREPT) techniques have successfully recovered the conductivity distribution at a Larmor-frequency. Methods: This work provides a non-invasive method to decompose the high-frequency conductivity into the extracellular medium conductivity based on a two-compartment model using multi-b diffusion-weighted imaging (Mb-DWI). To separate the intra- and extracellular micro-structures from the recovered high-frequency conductivity, we include higher b-values DWI and apply the random decision forests to stably determine the micro-structural diffusion parameters. Results: To demonstrate the proposed method, we conducted human experiments by comparing the results of reconstructed conductivity of extracellular medium and the conductivity in the intra-neurite and intra-cell body. Human experiments verify that the proposed method can recover the extracellular electrical properties from the high-frequency conductivity using a routine protocol sequence of MRI scan. Conclusion: We have proposed a method to decompose the electrical properties in the extracellular, intra-neurite, and soma compartments from the high-frequency conductivity map, reconstructed by solving the electro-magnetic equation with measured B1 phase signals.

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