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.

Distribution and metabolism of adrenocorticotropin in the rat

1979 ◽  
Vol 57 (9) ◽  
pp. 1024-1027 ◽  
Author(s):  
Maurice Normand ◽  
Josee Lalonde
Keyword(s):  
Standard Error ◽  
Time Course ◽  
Compartment Model ◽  
Sprague Dawley ◽  
Mean Values ◽  
Sprague Dawley Rats ◽  
Two Compartment Model ◽  
Rapid Fall ◽  
Significant Difference ◽  
Endogenous Release

The time course of plasma bioactive adrenocorticotropin (ACTH) concentrations measured following two rapid injections of the hormone at doses of 7.5 and 22.5 mU/100 g, iv, and one infusion over a period of 80 min at a rate of 1.3 mU/min per 100 g, to male Sprague–Dawley rats whose endogenous release of ACTH had been blocked, leads to the conclusion that the hormone is distributed in two compartments. Indeed, the rapid fall of plasma ACTH concentrations in the early minutes following either the injections or the stop of the infusion is followed by a much slower phase. There is no significant difference between the measurements and the two-compartment model outputs. The model represents, on the average, the mean values of the measurements plus or minus 1 standard error for the single injections and plus or minus 1.2 standard error for the infusion.

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.

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.

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.

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 Compromised dental cells viability following teeth-whitening exposure

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ola Redha ◽  
Morteza Mazinanian ◽  
Sabrina Nguyen ◽  
Dong Ok Son ◽  
Monika Lodyga ◽  
...  
Keyword(s):  
Protein Content ◽  
In Vitro Study ◽  
Organic Content ◽  
Time Dependent ◽  
Gingival Fibroblast ◽  
Direct Exposure ◽  
Significant Difference ◽  
Enamel Protein

AbstractThis study aimed to assess the viability of dental cells following time-dependent carbamide peroxide teeth-whitening treatments using an in-vitro dentin perfusion assay model. 30 teeth were exposed to 5% or 16% CP gel (4 h daily) for 2-weeks. The enamel organic content was measured with thermogravimetry. The time-dependent viability of human dental pulp stem cells (HDPSCs) and gingival fibroblast cells (HGFCs) following either indirect exposure to 3 commercially available concentrations of CP gel using an in-vitro dentin perfusion assay or direct exposure to 5% H2O2 were investigated by evaluating change in cell morphology and by hemocytometry. The 5% and 16% CP produced a significantly lower (p < 0.001) enamel protein content (by weight) when compared to the control. The organic content in enamel varied accordingly to the CP treatment: for the 16% and 5% CP treatment groups, a variation of 4.0% and 5.4%, respectively, was observed with no significant difference. The cell viability of HDPSCs decreased exponentially over time for all groups. Within the limitation of this in-vitro study, we conclude that even low concentrations of H2O2 and CP result in a deleterious change in enamel protein content and compromise the viability of HGFCs and HDPSCs. These effects should be observed in-vivo.

scholarly journals Robust Multi-TE ASL-Based Blood–Brain Barrier Integrity Measurements

2021 ◽  
Vol 15 ◽  
Author(s):  
Amnah Mahroo ◽  
Mareike Alicja Buck ◽  
Jörn Huber ◽  
Nora-Josefin Breutigam ◽  
Henk J. M. M. Mutsaerts ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Transit Time ◽  
Grey Matter ◽  
Compartment Model ◽  
Brain Barrier ◽  
Extended Model ◽  
Blood Brain ◽  
Two Compartment Model ◽  
Bbb Permeability

Multiple echo-time arterial spin labelling (multi-TE ASL) offers estimation of blood–tissue exchange dynamics by probing the T2 relaxation of the labelled spins. In this study, we provide a recipe for robust assessment of exchange time (Texch) as a proxy measure of blood–brain barrier (BBB) integrity based on a test-retest analysis. This includes a novel scan protocol and an extension of the two-compartment model with an “intra-voxel transit time” (ITT) to address tissue transit effects. With the extended model, we intend to separate the underlying two distinct mechanisms of tissue transit and exchange. The performance of the extended model in comparison with the two-compartment model was evaluated in simulations. Multi-TE ASL sequence with two different bolus durations was used to acquire in vivo data (n = 10). Cerebral blood flow (CBF), arterial transit time (ATT) and Texch were fitted with the two models, and mean grey matter values were compared. Additionally, the extended model also extracted ITT parameter. The test-retest reliability of Texch was assessed for intra-session, inter-session and inter-visit pairs of measurements. Intra-class correlation coefficient (ICC) and within-subject coefficient of variance (CoV) for grey matter were computed to assess the precision of the method. Mean grey matter Texch and ITT values were found to be 227.9 ± 37.9 ms and 310.3 ± 52.9 ms, respectively. Texch estimated by the extended model was 32.6 ± 5.9% lower than the two-compartment model. A significant ICC was observed for all three measures of Texch reliability (P &lt; 0.05). Texch intra-session CoV, inter-session CoV and inter-visit CoV were found to be 6.6%, 7.9%, and 8.4%, respectively. With the described improvements addressing intra-voxel transit effects, multi-TE ASL shows good reproducibility as a non-invasive measure of BBB permeability. These findings offer an encouraging step forward to apply this potential BBB permeability biomarker in clinical research.

ALFALFA SUPPLEMENTATION OF CORNCOB DIETS FOR SHEEP: EFFECT OF RUMINAL OR POSTRUMINAL SUPPLY OF PROTEIN ON INTAKE, DIGESTIBILITY, DIGESTA, PASSAGE AND LIVEWEIGHT CHANGES

1987 ◽  
Vol 67 (4) ◽  
pp. 1075-1082 ◽  
Author(s):  
L. R. NDLOVU ◽  
J. G. BUCHANAN-SMITH
Keyword(s):  
Soy Protein ◽  
Cell Walls ◽  
Dry Matter ◽  
Basal Diet ◽  
Compartment Model ◽  
Poor Quality ◽  
Latin Squares ◽  
Fecal Output ◽  
Single Compartment Model ◽  
Digesta Passage

In trial 1, nine wethers (18 mo old; 50 kg liveweight) fitted with tubes inserted into the abomasum, were assigned to three 3 × 3 Latin squares to determine effects of supplementing a basal diet of ground corncobs with either alfalfa (30% of dry matter intake) or soy protein (60 g d−1 infused postruminally). In each period, following determination of effect of supplementation on intake, digestibility and digesta passage were determined, the latter by pulse dosing with chromium mordanted cell walls from cobs through the feed. Total dry matter intakes were increased (P < 0.05) from 780 g d−1 to 1143 g d−1 by the supplements with a corresponding improvement in liveweight gain, but there was no difference between supplements. Apparent digestibilities of dry matter, organic matter and cell wall were decreased (P < 0.05) by alfalfa supplementation but not by soy protein infusion; however, intakes of digestible energy were identical for both supplements. Relative to the basal diet, alfalfa increased digesta passage but not rumen fill whereas infusion of soy protein increased digesta fill in the rumen but not digesta passage. In trial 2, addition of soy protein directly to the basal diet resulted in an intake similar to alfalfa supplementation (1154 vs. 1262 g dry matter d−1 respectively). Fecal output, estimated using a single compartment model to describe digesta passage through the tract, yielded results similar to those obtained by total collection. Key words: Roughage (poor quality), abomasal infusion, chromium-mordanted cell walls, fecal output estimation

scholarly journals Population Pharmacokinetic Analysis of Isoniazid, Acetylisoniazid, and Isonicotinic Acid in Healthy Volunteers

2015 ◽  
Vol 59 (11) ◽  
pp. 6791-6799 ◽  
Author(s):  
Kok-Yong Seng ◽  
Kim-Hor Hee ◽  
Gaik-Hong Soon ◽  
Nicholas Chew ◽  
Saye H. Khoo ◽  
...  
Keyword(s):  
Isonicotinic Acid ◽  
Compartment Model ◽  
Hepatic Function ◽  
Population Pharmacokinetic Analysis ◽  
Pharmacokinetic Analysis ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Mixed Effects Modeling ◽  
Two Compartment Model

ABSTRACTIn this study, we aimed to quantify the effects of theN-acetyltransferase 2 (NAT2) phenotype on isoniazid (INH) metabolismin vivoand identify other sources of pharmacokinetic variability following single-dose administration in healthy Asian adults. The concentrations of INH and its metabolites acetylisoniazid (AcINH) and isonicotinic acid (INA) in plasma were evaluated in 33 healthy Asians who were also given efavirenz and rifampin. The pharmacokinetics of INH, AcINH, and INA were analyzed using nonlinear mixed-effects modeling (NONMEM) to estimate the population pharmacokinetic parameters and evaluate the relationships between the parameters and the elimination status (fast, intermediate, and slow acetylators), demographic status, and measures of renal and hepatic function. A two-compartment model with first-order absorption best described the INH pharmacokinetics. AcINH and INA data were best described by a two- and a one-compartment model, respectively, linked to the INH model. In the final model for INH, the derived metabolic phenotypes for NAT2 were identified as a significant covariate in the INH clearance, reducing its interindividual variability from 86% to 14%. The INH clearance in fast eliminators was 1.9- and 7.7-fold higher than in intermediate and slow eliminators, respectively (65 versus 35 and 8 liters/h). Creatinine clearance was confirmed as a significant covariate for AcINH clearance. Simulations suggested that the current dosing guidelines (200 mg for 30 to 45 kg and 300 mg for >45 kg) may be suboptimal (3 mg/liter ≤Cmax≤ 6 mg/liter) irrespective of the acetylator class. The analysis established a model that adequately characterizes INH, AcINH, and INA pharmacokinetics in healthy Asians. Our results refine the NAT2 phenotype-based predictions of the pharmacokinetics for INH.

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