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

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.

1983 ◽  
Vol 244 (3) ◽  
pp. G314-G320 ◽  
Author(s):  
R. F. Bonewitz ◽  
E. C. Foulkes ◽  
E. J. O'Flaherty ◽  
V. S. Hertzberg

Effects of dexamethasone and adrenalectomy on the kinetics of jejunal 65Zn uptake and absorption were studied in the anesthetized adult rat. The jejunal lumen was perfused in situ with 5 mM glucose in 150 mM saline containing 65Zn and [14C]polyethylene glycol as volume marker. Over the 30-min perfusion period, the rate of net 65Zn removal from the perfusate was biexponential due to the establishment of a return flux to the lumen. An open two-compartment model satisfactorily describes these observations: (formula; see text) Dexamethasone (2 mg/kg ip 7 h before perfusion) increased k12 by 75% (P less than 0.0002) and decreased k20 by 45% (P less than 0.04). Both effects were independent of adrenalectomy. Mathematical simulations using the compartmental model and experimentally determined kinetic constants predicted that transfer of 65Zn into the body should be enhanced by adrenalectomy and retarded by dexamethasone administered to adrenalectomized rats. Dexamethasone and adrenalectomy thus differentially affect Zn uptake and absorption in this system, suggesting a possible adrenocortical hormone involvement in the regulation of Zn absorption. These changes are apparently not mediated via metallothionein.


1981 ◽  
Vol 59 (8) ◽  
pp. 794-799
Author(s):  
Jean-Pierre Caillé

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]


2018 ◽  
Vol 2018 ◽  
pp. 1-8
Author(s):  
Yan-Lin Liu ◽  
Jui-Ting Hsu ◽  
Tian-Yu Shih ◽  
Dmytro Luzhbin ◽  
Chun-Yuan Tu ◽  
...  

Objectives. Dual-energy X-ray absorptiometry (DXA) is frequently used to measure the areal bone mineral density (aBMD) in clinical practice. However, DXA measurements are affected by the bone thickness and the body size and are unable to indicate nonosseous areas within the trabecular bone. This study aims to quantify the volumetric bone mineral density (vBMD) using computed tomography (CT) images and the two-compartment model (TCM) methods. Methods. The TCM method was proposed and validated by dipotassium phosphate (K2HPO4) phantoms and a standard forearm phantom. 28 cases with DXA scans and pelvic CT scans acquired within six months were retrospectively collected. The vBMD calculated by TCM was compared with the aBMD obtained from DXA. Results. For the K2HPO4 phantoms with vBMD ranging from 0.135 to 0.467 g/cm3, the average difference between the real and calculated vBMD was 0.009 g/cm3 and the maximum difference was 0.019 g/cm3. For the standard forearm phantom with vBMD of 0.194, 0.103, and 0.054 g/cm3, the average differences between the real and calculated vBMD were 0.017, 0.014, and 0.011 g/cm3. In the clinical CT image validation, a good linear relationship between vBMD and aBMD was observed with the Pearson correlation coefficient of 0.920 (p<0.01). Conclusions. The proposed TCM method in combination with the homemade cortical bone equivalent phantom provides accurate quantification and spatial distribution of bone mineral content.


2019 ◽  
Vol 20 (2) ◽  
pp. 92-97
Author(s):  
M Amer ◽  
M Elsayed ◽  
S Kazawaki ◽  
W Fathy ◽  
Eman El-Ashry

The present study was performed to determine the pharmacokinetics of sulfamonomethoxine (20mg/kg) in 5 rabbits after its oral and intravenous administration. Blood samples were collected immediately before (time 0) and at 0.08, 0.25, 0.5, 1, 3, 5 and 8 hours post-dosing to evaluate the pharmacokinetics of sulfamonomethoxine. Plasma sulfamonomethoxine concentrations were quantified with HPLC-UV, and plasma drug concentration versus time data after IV was best fitted to the two-compartment model, characterized with the distribution phase (α) equaled to 2.05 h-1 with a distribution half-life [t0.5(α)] equaled to 0.61 h. The volume of distribution of (V1c) was 0.15 ml/kg., whereas the volume of distribution at a steady – state [Vdss] was 0.20 ml/kg, and the body clearance was 0.03 ml/ kg / h. After oral administration of SMM, plasma drug concentrations were best fitted to a two-compartment model, of which the mean half-life of absorption (t1/2ab) and elimination (t1/2β) were 0.02 and 1.99 h, respectively. The maximal absorption concentration (Cmax) was estimated as 114.06 µg/ml at 0.12 h, and the Area under the curve (AUC) was 340.42 µg/ml/h.


PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e12409
Author(s):  
J. Alexander Bonanno ◽  
Nancy E. Breen ◽  
Michael F. Tlusty ◽  
Lawrence Andrade ◽  
Andrew L. Rhyne

The illegal practice of cyanide fishing continues throughout the Indo-Pacific. To combat this destructive fishing method, a reliable test to detect whether a fish has been captured using cyanide (CN) is needed. We report on the toxicokinetics of acute, pulsed CN exposure and chronic thiocyanate (SCN) exposure, the major metabolite of CN, in the clownfish species, Amphiprion clarkii. Fish were pulse exposed to 50 ppm CN for 20 or 45 s or chronically exposed to 100 ppm SCN for 12 days and blood plasma levels of SCN were measured. SCN blood plasma levels reached a maximum concentration (301–468 ppb) 0.13–0.17 days after exposure to CN and had a 0.1 to 1.2 day half-life. The half-life of blood plasma SCN after chronic exposure to SCN was found to be 0.13 days. Interestingly, we observed that when a fish, with no previous CN or SCN exposure, was placed in holding water spiked to 20 ppb SCN, there was a steady decrease in the SCN concentration in the holding water until it could no longer be detected at 24 hrs. Under chronic exposure conditions (100 ppm, 12 days), trace levels of SCN (∼40 ppb) were detected in the holding water during depuration but decreased to below detection within the first 24 hrs. Our holding water experiments demonstrate that low levels of SCN in the holding water of A. clarkii will not persist, but rather will quickly and steadily decrease to below detection limits refuting several publications. After CN exposure, A. clarkii exhibits a classic two compartment model where SCN is eliminated from the blood plasma and is likely distributed throughout the body. Similar studies of other species must be examined to continue to develop our understanding of CN metabolism in marine fish before a reliable cyanide detection test can be developed.


1998 ◽  
Vol 9 (1) ◽  
pp. 128-132
Author(s):  
S W Smye ◽  
E J Lindley ◽  
E J Will

A two-compartment model of urea kinetics during hemodialysis is used to predict the effect of exercise on hemodialysis dose. It is assumed that the two compartments represent tissues that are perfused by low and high blood flows (initially 1.1 L/min and 3.8 L/min). The effect of changing the distribution of flows between the compartments, emulating the effect of exercise, is simulated using the model equations for a range of dialyzer clearances. Compartmental volumes are assumed constant (33.4 L and 8.6 L for low- and high-flow compartments, respectively). The analysis identifies muscle perfusion as a rate-limiting factor during the later stages of hemodialysis and illustrates the benefit of exercise during this phase in increasing dialysis efficiency. The model suggests that the postdialysis rebound in the blood urea concentration is eliminated by increasing flow to the low-flow compartment from 1.1 L/min to 7.1 L/min and sustaining this for at least 30 min of a 150-min dialysis session, independent of the dialyzer clearance. Additional exercise will not increase the dialysis dose. Experimental studies are required to confirm the analysis.


2001 ◽  
Vol 40 (01) ◽  
pp. 31-37 ◽  
Author(s):  
U. Wellner ◽  
E. Voth ◽  
H. Schicha ◽  
K. Weber

Summary Aim: The influence of physiological and pharmacological amounts of iodine on the uptake of radioiodine in the thyroid was examined in a 4-compartment model. This model allows equations to be derived describing the distribution of tracer iodine as a function of time. The aim of the study was to compare the predictions of the model with experimental data. Methods: Five euthyroid persons received stable iodine (200 μg, 10 mg). 1-123-uptake into the thyroid was measured with the Nal (Tl)-detector of a body counter under physiological conditions and after application of each dose of additional iodine. Actual measurements and predicted values were compared, taking into account the individual iodine supply as estimated from the thyroid uptake under physiological conditions and data from the literature. Results: Thyroid iodine uptake decreased from 80% under physiological conditions to 50% in individuals with very low iodine supply (15 μg/d) (n = 2). The uptake calculated from the model was 36%. Iodine uptake into the thyroid did not decrease in individuals with typical iodine supply, i.e. for Cologne 65-85 μg/d (n = 3). After application of 10 mg of stable iodine, uptake into the thyroid decreased in all individuals to about 5%, in accordance with the model calculations. Conclusion: Comparison of theoretical predictions with the measured values demonstrated that the model tested is well suited for describing the time course of iodine distribution and uptake within the body. It can now be used to study aspects of iodine metabolism relevant to the pharmacological administration of iodine which cannot be investigated experimentally in humans for ethical and technical reasons.


2018 ◽  
Vol 6 (9) ◽  
Author(s):  
DR.MATHEW GEORGE ◽  
DR.LINCY JOSEPH ◽  
MRS.DEEPTHI MATHEW ◽  
ALISHA MARIA SHAJI ◽  
BIJI JOSEPH ◽  
...  

Blood pressure is the force of blood pushing against blood vessel walls as the heart pumps out blood, and high blood pressure, also called hypertension, is an increase in the amount of force that blood places on blood vessels as it moves through the body. Factors that can increase this force include higher blood volume due to extra fluid in the blood and blood vessels that are narrow, stiff, or clogged(1). High blood pressure can damage blood vessels in the kidneys, reducing their ability to work properly. When the force of blood flow is high, blood vessels stretch so blood flows more easily. Eventually, this stretching scars and weakens blood vessels throughout the body, including those in the kidneys.


Author(s):  
Dmitriy Antipin ◽  
Vladimir Vorobev ◽  
Denis Bondarenko ◽  
Gennadiy Petrov

The analysis of the design features of the bogie of the TEM23 shunting diesel locomotive is carried out. In the process of analysis, the directions of its improvement are determined. It is proposed to rotate the bogie frame in the vertical plane by reducing the body supports to two and using a pivot with low lowering, equip the bogies with pneumatic spring suspension in the form of two corrugations installed in series with shortened suspension springs. The proposed options for improving the undercarriage of a diesel locomotive will increase the competitiveness of products and reduce costs


2020 ◽  
Author(s):  
Andri Nirwana

Abstract: The phenomenon of the people who forcibly took covid's corpse 19 from the hospital to be taken care of by Fardhu Kifayah by his family and the community, became a conclusion that there was community doubt about the management of Tajhiz Mayat conducted by the hospital. Coupled with the circulation of the video of the Ruku movement 'in the corpse prayer conducted by unscrupulous parties at the Hospital, became added doubts from the public against the hospital. To solve this problem, this research uses a Descriptive Analysis approach, namely by formulating a question, namely How to arrange Covid 19's body in Banda Aceh and this question will be answered with several theories and data sets from the field. So it was concluded in a conclusion that answered the formulation of the problems mentioned. Theoretically the spread of covid 19 is very fast, the size of the virus is only 0.1 micrometer and is in body fluids, especially nasopharyngeal fluid and oropharyngeal fluids of infected people, fluids in the body of covid 19 bodies can get out through every gap of the body such as mouth, nose, eye and rectum, because it requires special techniques in its management. Fardhu kifayah to covid 19 bodies should be carried out by trained Ustad and trained health workers, so that the spread stopped. The results of this study concluded that the management of the Moslem bodies died at Zainal Abidin Hospital in Banda Aceh was in accordance with the Fatwa of the Aceh Ulama Council (MPU) and the bodies were handled by trained Ustad and health workers.


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