Time-dependent kinetics. V: Time course of drug levels during enzyme induction (one-compartment model)

1979 ◽  
Vol 7 (6) ◽  
pp. 557-578 ◽  
Author(s):  
René H. Levy ◽  
Martin S. Dumain ◽  
James L. Cook
Keyword(s):  
Enzyme Induction ◽  
Time Course ◽  
Compartment Model ◽  
Time Dependent ◽  
Drug Levels

Influence of stable iodine on the uptake of the thyroid – model vs. experiment

2001 ◽  
Vol 40 (01) ◽  
pp. 31-37 ◽  
Author(s):  
U. Wellner ◽  
E. Voth ◽  
H. Schicha ◽  
K. Weber
Keyword(s):  
Time Course ◽  
Compartment Model ◽  
The Body ◽  
Iodine Uptake ◽  
Model Calculations ◽  
Physiological Conditions ◽  
Iodine Supply ◽  
Predicted Values ◽  
The Individual ◽  
Stable Iodine

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.

scholarly journals Nonlinear Compartment Models with Time-Dependent Parameters

Mathematics ◽  
2021 ◽  
Vol 9 (14) ◽  
pp. 1657
Author(s):  
Jochen Merker ◽  
Benjamin Kunsch ◽  
Gregor Schuldt
Keyword(s):  
Stable Equilibrium ◽  
Compartment Model ◽  
Basins Of Attraction ◽  
Dynamical Behaviour ◽  
Time Dependent ◽  
Compartment Models ◽  
Autonomous Case ◽  
Hyperbolic Equilibrium ◽  
Interior Points ◽  
Two Parameter

A nonlinear compartment model generates a semi-process on a simplex and may have an arbitrarily complex dynamical behaviour in the interior of the simplex. Nonetheless, in applications nonlinear compartment models often have a unique asymptotically stable equilibrium attracting all interior points. Further, the convergence to this equilibrium is often wave-like and related to slow dynamics near a second hyperbolic equilibrium on the boundary. We discuss a generic two-parameter bifurcation of this equilibrium at a corner of the simplex, which leads to such dynamics, and explain the wave-like convergence as an artifact of a non-smooth nearby system in C0-topology, where the second equilibrium on the boundary attracts an open interior set of the simplex. As such nearby idealized systems have two disjoint basins of attraction, they are able to show rate-induced tipping in the non-autonomous case of time-dependent parameters, and induce phenomena in the original systems like, e.g., avoiding a wave by quickly varying parameters. Thus, this article reports a quite unexpected path, how rate-induced tipping can occur in nonlinear compartment models.

Pulsatile Pressure and Flow in the Skeletal Muscle Microcirculation

1990 ◽  
Vol 112 (4) ◽  
pp. 437-443 ◽  
Author(s):  
Shou-Yan Lee ◽  
G. W. Schmid-Scho¨nbein
Keyword(s):  
Skeletal Muscle ◽  
Arterial Pressure ◽  
Time Course ◽  
Venous Pressure ◽  
Time Dependent ◽  
Physiological Importance ◽  
Pulsatile Pressure ◽  
Theoretical Predictions ◽  
Skeletal Muscle Microcirculation

Although blood flow in the microcirculation of the rat skeletal muscle has negligible inertia forces with very low Reynolds number and Womersley parameter, time-dependent pressure and flow variations can be observed. Such phenomena include, for example, arterial flow overshoot following a step arterial pressure, a gradual arterial pressure reduction for a step flow, or hysteresis between pressure and flow when a pulsatile pressure is applied. Arterial and venous flows do not follow the same time course during such transients. A theoretical analysis is presented for these phenomena using a microvessel with distensible viscoelastic walls and purely viscous flow subject to time variant arterial pressures. The results indicate that the vessel distensibility plays an important role in such time-dependent microvascular flow and the effects are of central physiological importance during normal muscle perfusion. In-vivo whole organ pressure-flow data in the dilated rat gracilis muscle agree in the time course with the theoretical predictions. Hemodynamic impedances of the skeletal muscle microcirculation are investigated for small arterial and venous pressure amplitudes superimposed on an initial steady flow and pressure drop along the vessel.

Time-dependent progression of neurogenic lower urinary tract dysfunction after spinal cord injury in the mouse model

2021 ◽  
Author(s):  
Tetsuichi Saito ◽  
Daisuke Gotoh ◽  
Naoki Wada ◽  
Pradeep Tyagi ◽  
Tomonori Minagawa ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Spinal Cord Injury ◽  
Time Course ◽  
Time Dependent ◽  
Lower Urinary Tract Dysfunction ◽  
Emg Activity ◽  
Mrna Levels ◽  
Mechanosensitive Channels ◽  
Reduction Time ◽  
Cord Injury

This study evaluated the time-course changes in bladder and external urinary sphincter (EUS) activity as well as the expression of mechanosensitive channels in lumbosacral dorsal root ganglia (DRG) after spinal cord injury (SCI). Female C57BL/6N mice in the SCI group underwent transection of the Th8/9 spinal cord. Spinal intact mice and SCI mice at 2, 4 and 6 weeks post SCI were evaluated by single-filling cystometry and EUS-electromyography (EMG). In another set of mice, the bladder and L6-S1 DRG were harvested for protein and mRNA analyses. In SCI mice, non-voiding contractions was confirmed at 2 weeks post-SCI, and did not increase over time to 6 weeks. In 2-weeks SCI mice, EUS-EMG measurements revealed detrusor-sphincter dyssynergia (DSD), but periodic EMG reductions during bladder contraction were hardly observed. At 4 weeks, SCI mice showed increases of EMG activity reduction time with increased voiding efficiency (VE). At 6 weeks, SCI mice exhibited a further increase in EMG reduction time. RT-PCR of L6-S1 DRG showed increased mRNA levels of TRPV1 and ASIC1-3 in SCI mice with a decrease of ASIC2-3 at 6 weeks compared to 4 weeks whereas Piezo2 showed a slow increase at 6 weeks. Protein assay showed the SCI-induced overexpression of bladder BDNF with a time-dependent decrease post SCI. These results indicate that detrusor overactivity is established in the early phase whereas DSD is completed later at 4 weeks with an improvement at 6 weeks post SCI, and that mechanosensitive channels may be involved in the time-dependent changes.

Estimation of the rate of appearance in the non-steady state with a two-compartment model

1992 ◽  
Vol 263 (2) ◽  
pp. E400-E415 ◽  
Author(s):  
A. Mari
Keyword(s):  
Steady State ◽  
Time Course ◽  
Specific Activity ◽  
Glucose Production ◽  
Compartment Model ◽  
New Method ◽  
Two Compartment Model ◽  
Glucose Clamp Technique ◽  
Glucose Output ◽  
The Relationship

A simple tracer-based method for calculating the rate of appearance of endogenous substances in the non-steady state, free from the inconsistencies of Steele's equation, is still lacking. This paper presents a method based on a two-compartment model by which the rate of appearance can be calculated with only a modest increase in complexity over Steele's approach. An equation is developed where the rate of appearance is expressed as a sum of three terms: a steady-state term, a term for the first compartment, and a term for the second compartment. The formula employs three parameters and makes the relationship between rate of appearance and specific activity changes explicit. An equation is also provided for estimating the error of the method in each individual run. The algorithm can be implemented with a spreadsheet on a personal computer. Simulated and experimental data obtained by the hyperinsulinemic euglycemic glucose clamp technique were used as a test. The accuracy with which the time course of glucose production could be reconstructed was clearly better than that using Steele's equation. Marked negative values for endogenous glucose output were calculated with Steele's equation but not with the new method. The characteristics of generality, simplicity, and accuracy and the availability of an error estimate make this new method suitable for routine application to non-steady-state tracer analysis.

scholarly journals Modeling Growth, Containment and Decay of the COVID-19 Epidemic in Italy

2020 ◽  
Vol 8 ◽  
Author(s):  
Francesco Capuano
Keyword(s):  
Exponential Growth ◽  
Compartment Model ◽  
Growth Behavior ◽  
Time Dependent ◽  
Model Parameters ◽  
Susceptible Population ◽  
Dependent Rate ◽  
Slow Decay ◽  
Cumulative Curve ◽  
Modeling Growth

A careful inspection of the cumulative curve of confirmed COVID-19 infections in Italy and in other hard-hit countries reveals three distinct phases: i) an initial exponential growth (unconstrained phase), ii) an algebraic, power-law growth (containment phase), and iii) a relatively slow decay. We propose a parsimonious compartment model based on a time-dependent rate of depletion of the susceptible population that captures all such phases for a plausible range of model parameters. The results suggest an intimate interplay between the growth behavior, the timing and implementation of containment strategies, and the subsequent saturation of the outbreak.

scholarly journals Population Pharmacokinetics of Oseltamivir: Pediatrics through Geriatrics

2013 ◽  
Vol 57 (8) ◽  
pp. 3470-3477 ◽  
Author(s):  
Mohamed A. Kamal ◽  
Scott A. Van Wart ◽  
Craig R. Rayner ◽  
Vishak Subramoney ◽  
Daniel K. Reynolds ◽  
...  
Keyword(s):  
Steady State ◽  
Time Course ◽  
Demographic Data ◽  
Visual Predictive Check ◽  
Compartment Model ◽  
Plasma Drug ◽  
First Order ◽  
Drug Concentrations ◽  
Population Pk ◽  
The Impact

ABSTRACTOseltamivir is a potent inhibitor of influenza virus neuraminidase enzymes essential for viral replication. This study aimed to investigate the impact of covariates on pharmacokinetic (PK) variability of oseltamivir and its active metabolite form, oseltamivir carboxylate (OC). Dosing history, plasma drug concentrations, and demographic information were pooled from 13 clinical trials providing data for 390 healthy and infected subjects ranging in age from 1 to 78 years and given oseltamivir doses of 20 to 1,000 mg. Candidate population PK models simultaneously characterizing the time course of oseltamivir and OC in plasma were evaluated by using the NONMEM software program, and subject covariates were assessed using stepwise forward selection (α = 0.01) and backward elimination (α = 0.001). A two-compartment model with first-order absorption of oseltamivir and first-order conversion of oseltamivir to OC and a one-compartment model with first-order elimination of OC were utilized. Body weight when evaluated using a power function was a significant predictor of the apparent oseltamivir clearance and both apparent OC clearance (CLm/F) and central volume of distribution (Vcm/F). Creatinine clearance was a significant predictor of CLm/F, while Vcm/F also decreased linearly with age. A visual predictive check indicated that the final model described oseltamivir and OC concentrations in plasma adequately across dose regimens and subject covariate ranges. Concordance of population mean and individualpost hocpredictions of maximum concentration of drug at steady state (Cmax) and area under the plasma drug concentration-time curve from 0 to 24 h at steady state (AUC0–24) was high (r2= 0.81 and 0.71, respectively). In conclusion, a comprehensive population PK model was constructed to bridge the adult to pediatric oseltamivir PK data, allowing for reasonable estimation of the PK of OC using subject demographic data alone.

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