Assessment of methods for improving tracer estimation of non-steady-state rate of appearance

1999 ◽  
Vol 87 (5) ◽  
pp. 1813-1822 ◽  
Author(s):  
A. Gastaldelli ◽  
A. R. Coggan ◽  
R. R. Wolfe
Keyword(s):  
Steady State ◽  
Infusion Rate ◽  
Traditional Approach ◽  
Volume Of Distribution ◽  
Constant Volume ◽  
Constant Infusion ◽  
Steady State Condition ◽  
Fixed Volume ◽  
The One ◽  
Infusion Technique

The most common approach for estimating substrate rate of appearance (Ra) is use of the single-pool model first proposed by R. W. Steele, J. S. Wall, R. C. DeBodo, and N. Altszuler. ( Am. J. Physiol. 187: 15–24, 1956). To overcome the model error during highly non-steady-state conditions due to the assumption of a constant volume of distribution (V), two strategies have been proposed: 1) use of a variable tracer infusion rate to minimize tracer-to-tracee ratio (TTR) variations (fixed-volume approach) or 2) use of two tracers of the same substrate with one infused at a constant rate and the other at a variable rate (variable-volume approach or approach of T. Issekutz, R. Issekutz, and D. Elahi. Can. J. Physiol. Pharmacol. 52: 215–224, 1974). The goal of this study was to compare the results of these two strategies for the analysis of the kinetics of glycerol and glucose under the non-steady-state condition created by a constant infusion of epinephrine (50 ng ⋅ kg−1 ⋅ min−1) with the traditional approach of Steele et al., which uses a constant infusion and fixed volume. The results showed that for glucose and glycerol the estimates of Raobtained with the constant and the variable tracer infusion rate and the equation of Steele et al. were comparable. The variable tracer infusion approach was less sensitive to the choice of V in estimating Ra for glycerol and glucose, although the advantage of changing the tracer infusion rate was greater for glucose than for glycerol. The model of Issekutz et al. showed instability when the ratio TTR1/TTR2approaches a constant value, and the model is more sensitive to measurement error than the constant-volume model for glucose and glycerol. We conclude that the one-tracer constant-infusion technique is sufficient in most cases for glycerol, whereas the one-tracer variable-infusion technique is preferable for glucose. Reasonable values for glucose Ra can be obtained with the constant-infusion technique if V = 145 ml/kg.

Changes in glycerol kinetics after E. coli endotoxin administration in dogs

1984 ◽  
Vol 246 (3) ◽  
pp. R325-R330
Author(s):  
O. P. McGuinness ◽  
J. J. Spitzer
Keyword(s):  
Steady State ◽  
Infusion Rate ◽  
Volume Of Distribution ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Glycerol Concentration ◽  
Endotoxin Administration ◽  
E Coli ◽  
The Face ◽  
Anesthetized Dogs

The metabolic clearance rate (MCR) and maximal rate of glycerol removal (Rd max) were determined in anesthetized dogs at two time periods after the intravenous administration of either Escherichia coli endotoxin or saline. The nonisotopic method employed in these studies to determine the MCR of glycerol consisted of a constant infusion of glycerol at three different infusion rates. At each infusion rate a steady-state glycerol concentration was obtained. The reciprocal of the slope of the linear relationship between the glycerol infusion rate and the change in the steady-state arterial glycerol concentration was equal to the MCR of glycerol. Administration of endotoxin significantly decreased the MCR of glycerol, whereas the volume of distribution of glycerol was not altered significantly. The arterial glycerol turnover remained unaltered, whereas arterial glycerol concentration increased after endotoxin administration. The studies demonstrate that the elevated arterial glycerol concentration maintained the rate of glycerol turnover in the face of decreased efficiency of glycerol removal after endotoxin administration.

scholarly journals Synovial and Systemic Pharmacokinetics of Florfenicol and PK/PD Integration against Streptococcus suis in Pigs

Pharmaceutics ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 109
Author(s):  
Zoltán Somogyi ◽  
Patrik Mag ◽  
Dóra Kovács ◽  
Ádám Kerek ◽  
Pál Szabó ◽  
...  
Keyword(s):  
Steady State ◽  
Synovial Fluid ◽  
Dosage Regimen ◽  
Multiple Reaction Monitoring ◽  
Area Under The Curve ◽  
Pharmacokinetic Profile ◽  
Volume Of Distribution ◽  
Clinical Samples ◽  
Therapeutic Success ◽  
Steady State Condition

Florfenicol is a member of the phenicol group, a broad-spectrum antibacterial agent. It has been used for a long time in veterinary medicine, but there are some factors regarding its pharmacokinetic characteristics that have yet to be elucidated. The aim of our study was to describe the pharmacokinetic profile of florfenicol in synovial fluid and plasma of swine after intramuscular (i.m.) administration. In addition, the dosage regimen of treatment of arthritis caused by S. suis was computed for florfenicol using pharmacokinetic/pharmacodynamic (PK/PD) indices. As the first part of our investigation, the pharmacokinetic (PK) parameters of florfenicol were determined in the plasma and synovial fluid of six pigs. Following drug administration (15 mg/kgbw, intramuscularly), blood was drawn at the following times: 10, 20, 30, 40, 50 and 60 min, 2, 3, 4, 5, 6, 7, 8, 12, 24, 48 and 72 h; synovial fluid samples were taken after 1, 2, 3, 4, 6, 8, 12, 24, 48 and 72 h. The concentration of florfenicol was determined by a validated liquid chromatography-mass spectrometry (LC-MS/MS) method via multiple reaction monitoring (MRM) modes. As the second part of our research, minimum inhibitory concentration (MIC) values of florfenicol were determined in 45 S. suis strains isolated from clinical samples collected in Hungary. Furthermore, a strain of S. suis serotype 2 (SS3) was selected, and killing-time curves of different florfenicol concentrations (0.5 µg/mL, 1 µg/mL and 2 µg/mL) were determined against this strain. Peak concentration of the florfenicol was 3.58 ± 1.51 µg/mL in plasma after 1.64 ± 1.74 h, while it was 2.73 ± 1.2 µg/mL in synovial fluid 3.4 ± 1.67 h after administration. The half-life in plasma was found to be 17.24 ± 9.35 h, while in synovial fluid it was 21.01 ± 13.19 h. The area under the curve (AUC24h) value was 54.66 ± 23.34 μg/mL·h for 24 h in plasma and 31.24 ± 6.82 μg/mL·h for 24 h in synovial fluid. The drug clearance scaled by bioavailability (Cl/F) in plasma and synovial fluid was 0.19 ± 0.08 L/h/kg and 0.29 ± 0.08 L/h/kg, respectively. The mean residence time (MRT) in plasma and synovial fluid was 24.0 ± 13.59 h and 27.39 ± 17.16 h, respectively. The steady-state volume of distribution (Vss) in plasma was calculated from Cl/F of 0.19 ± 0.08 L/h/kg, multiplied by MRT of 24.0 ± 13.59 h. For the PK/PD integration, average plasma and synovial fluid concentration of florfenicol was used in a steady-state condition. The obtained MIC50 value of the strains was 2.0 µg/mL, and MIC90 proved to be 16.0 µg/mL. PK/PD integration was performed considering AUC24h/MIC breakpoints that have already been described. This study is the first presentation of the pharmacokinetic behavior of florfenicol in swine synovia as well as a recommendation of extrapolated critical MICs of S. suis for therapeutic success in the treatment of S. suis arthritis in swine, but it should be noted that this requires a different dosage regimen to that used in authorized florfenicol formulations.

scholarly journals Impact of Albumin and Omeprazole on Steady-State Population Pharmacokinetics of Voriconazole and Development of a Voriconazole Dosing Optimization Model in Thai Patients with Hematologic Diseases

Antibiotics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 574
Author(s):  
Buddharat Khan-asa ◽  
Baralee Punyawudho ◽  
Noppaket Singkham ◽  
Piyawat Chaivichacharn ◽  
Ekapun Karoopongse ◽  
...  
Keyword(s):  
Steady State ◽  
Compartment Model ◽  
Apparent Volume ◽  
Volume Of Distribution ◽  
Albumin Level ◽  
Hematologic Diseases ◽  
Mixed Effects Modeling ◽  
Dosing Regimens ◽  
The One ◽  
Dosing Optimization

This study aimed to identify factors that significantly influence the pharmacokinetics of voriconazole in Thai adults with hematologic diseases, and to determine optimal voriconazole dosing regimens. Blood samples were collected at steady state in 65 patients (237 concentrations) who were taking voriconazole to prevent or treat invasive aspergillosis. The data were analyzed using a nonlinear mixed-effects modeling approach. Monte Carlo simulation was applied to optimize dosage regimens. Data were fitted with the one-compartment model with first-order absorption and elimination. The apparent oral clearance (CL/F) was 3.43 L/h, the apparent volume of distribution (V/F) was 47.6 L, and the absorption rate constant (Ka) was fixed at 1.1 h−1. Albumin and omeprazole ≥ 40 mg/day were found to significantly influence CL/F. The simulation produced the following recommended maintenance doses of voriconazole: 50, 100, and 200 mg every 12 h for albumin levels of 1.5–3, 3.01–4, and 4.01–4.5 g/dL, respectively, in patients who receive omeprazole ≤ 20 mg/day. Patients who receive omeprazole ≥ 40 mg/day and who have serum albumin level 1.5–3 and 3.01–4.5 g/dL should receive voriconazole 50 and 100 mg, every 12 h, respectively. Albumin level and omeprazole dosage should be carefully considered when determining the appropriate dosage of voriconazole in Thai patients.

Arginine vasopressin metabolism in dogs. I. Evidence for a receptor-mediated mechanism.

1978 ◽  
Vol 235 (6) ◽  
pp. E591 ◽  
Author(s):  
R E Weitzman ◽  
D A Fisher
Keyword(s):  
Arginine Vasopressin ◽  
Urine Osmolality ◽  
Volume Of Distribution ◽  
Membrane Receptors ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Strong Negative Correlation ◽  
Pulse Injection ◽  
Plasma Membrane Receptors ◽  
Infusion Technique

The plasma clearance rates (PCR) of arginine vasopressin (AVP), and iodinated AVP (125I-AVP) were determined after pulse injection in conscious water-loaded dogs. Both the PCR and the apparent initial volume of distribution were significantly greater for AVP than for the biologically inactive iodinated AVP 37.4 +/- 4.8 ml/kg per min vs. 6.7 +/- 0.8 ml/kg per min (P less than 0.001) and 12.7 +/- 0.9% body wt vs. 7.1 +/- 0.4% body wt (P less than 0.001). AVP clearance was then determined by the constant-infusion technique at doses that produced equilibrium AVP concentrations within and above the physiological range. AVP-PCR was 37.4 +/- 7.1 ml/kg per min at 34 microU/kg per min, which was comparable to that after pulse injection (P less than 0.9). AVP clearance fell progressively, and urine osmolality progressively increased with increasing AVP infusion rates to plateau values at 136 microU/kg per min; a strong negative correlation was observed between mean AVP-PCR and urine osmolality (r = -0.993). The data suggest a relationship between the biological activity of AVP and its clearance. It is proposed that plasma membrane receptors may mediate a portion of the metabolic clearance of AVP.

Drawbacks of the constant-infusion technique for measurement of renal function

1995 ◽  
Vol 268 (4) ◽  
pp. F543-F552 ◽  
Author(s):  
B. A. Van Acker ◽  
G. C. Koomen ◽  
L. Arisz
Keyword(s):  
Renal Function ◽  
Steady State ◽  
Plasma Concentrations ◽  
Constant Infusion ◽  
Urinary Recovery ◽  
Infusion Method ◽  
Pah Clearance ◽  
The Difference ◽  
Infusion Technique ◽  
Extrarenal Clearance

We investigated the validity of the steady-state constant infusion method (CIM), in which quantitative urinary recovery and constant plasma concentrations of the solute infused are required. Successive 3-h clearances of inulin and p-aminohippuric acid (PAH) were determined for 27 h in 25 patients with renal disease. Results were compared with the standard method of bladder clearance (StM) and with a modified CIM (ModCIM). The 24-h urinary recovery was incomplete for both inulin and PAH. Mean 24-h ModCIM inulin clearance overestimated StM by 4.5 ml.min-1 x 1.73 m-2 (range 0–9, P < 0.001) independent of the extent of renal impairment and pointed to slow distribution and/or extrarenal clearance of inulin. For PAH, the difference between ModCIM and StM clearance was related to the average PAH clearance by ModCIM and StM (r = 0.78). Furthermore, neither plasma inulin nor PAH became completely constant, because of the circadian rhythm in renal function. In conclusion, the conditions of the steady-state CIM technique are not fulfilled, and the method is not suitable for accurate measurement of inulin and PAH clearance, especially when the clearance is low.

Continuous Estimation of CO2 Production during Exercise

1997 ◽  
Vol 36 (04/05) ◽  
pp. 368-371
Author(s):  
R. Soma ◽  
Y. Yamamoto
Keyword(s):  
Fuzzy Logic ◽  
Steady State ◽  
Infusion Rate ◽  
Feedback System ◽  
Whole Body ◽  
Co2 Production ◽  
Cycle Exercise ◽  
Continuous Estimation ◽  
Breath Measurement ◽  
13Co2 Enrichment

Abstract.A new method was developed for continuous isotopic estimation of human whole body CO2 rate of appearance (Ra) during non-steady state exercise. The technique consisted of a breath-by-breath measurement of 13CO2 enrichment (E) and a real-time fuzzy logic feedback system which controlled NaH13CO3 infusion rate to achieve an isotopic steady state. Ra was estimated from the isotope infusion rate and body 13CO2 enrichment which was equal to E at the isotopic steady state. During a non-steady state incremental cycle exercise (5 w/min or 10 w/min), NaH13CO3 infusion rate was successfully increased by the action of feedback controller so as to keep E constant.

scholarly journals Computational Performance of Disparate Lattice Boltzmann Scenarios under Unsteady Thermal Convection Flow and Heat Transfer Simulation

Computation ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 65
Author(s):  
Aditya Dewanto Hartono ◽  
Kyuro Sasaki ◽  
Yuichi Sugai ◽  
Ronald Nguele
Keyword(s):  
Heat Transfer ◽  
Steady State ◽  
Natural Convection ◽  
Lattice Boltzmann ◽  
Numerical Results ◽  
Convection And Heat Transfer ◽  
Steady State Condition ◽  
Physical Systems ◽  
Flow And Heat Transfer ◽  
Computational Performance

The present work highlights the capacity of disparate lattice Boltzmann strategies in simulating natural convection and heat transfer phenomena during the unsteady period of the flow. Within the framework of Bhatnagar-Gross-Krook collision operator, diverse lattice Boltzmann schemes emerged from two different embodiments of discrete Boltzmann expression and three distinct forcing models. Subsequently, computational performance of disparate lattice Boltzmann strategies was tested upon two different thermo-hydrodynamics configurations, namely the natural convection in a differentially-heated cavity and the Rayleigh-Bènard convection. For the purposes of exhibition and validation, the steady-state conditions of both physical systems were compared with the established numerical results from the classical computational techniques. Excellent agreements were observed for both thermo-hydrodynamics cases. Numerical results of both physical systems demonstrate the existence of considerable discrepancy in the computational characteristics of different lattice Boltzmann strategies during the unsteady period of the simulation. The corresponding disparity diminished gradually as the simulation proceeded towards a steady-state condition, where the computational profiles became almost equivalent. Variation in the discrete lattice Boltzmann expressions was identified as the primary factor that engenders the prevailed heterogeneity in the computational behaviour. Meanwhile, the contribution of distinct forcing models to the emergence of such diversity was found to be inconsequential. The findings of the present study contribute to the ventures to alleviate contemporary issues regarding proper selection of lattice Boltzmann schemes in modelling fluid flow and heat transfer phenomena.

Resistance to Outflow of Cerebrospinal Fluid Determined by Bolus Injection Technique and Constant Rate Steady State Infusion in Humans

Neurosurgery ◽  
1985 ◽  
Vol 16 (3) ◽  
pp. 336-340 ◽  
Author(s):  
Michael Kosteljanetz
Keyword(s):  
Cerebrospinal Fluid ◽  
Steady State ◽  
Bolus Injection ◽  
Point Of View ◽  
Injection Technique ◽  
Communicating Hydrocephalus ◽  
Constant Rate ◽  
High Degree ◽  
Infusion Technique

Abstract Two methods for the determination of resistance to the outflow of cerebrospinal fluid, the bolus injection technique and the constant rate steady state infusion technique, were compared. Thirty-two patients with a variety of intracranial diseases (usually communicating hydrocephalus) were studied. There was a high degree of correlation between the resistance values obtained with the two methods, but values based on the bolus injection technique were systematically and statistically significantly lower than those obtained with the constant rate infusion test. From a practical point of view. both methods were found to be applicable in a clinical setting.

Continuous determination of the volume of a space in a non steady state condition

1974 ◽  
Vol 36 (1) ◽  
pp. 59-66
Author(s):  
Oscar A. Gómez-Poviña ◽  
Carmen Sainz de Calatroni ◽  
Susana Orden de Puhl ◽  
Mariano J. Guerrero
Keyword(s):  
Steady State ◽  
State Condition ◽  
Steady State Condition ◽  
Continuous Determination
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