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PubMed2003

An approach to predict the ductus-arteriosus dilating effect induced by lipo-prostaglandin E1 in newborn rats lacking plasma concentration-time data by the pharmacological response kinetic model.

The usefulness of kinetic analysis of pharmacological response data was discussed in investigating the ductus arteriosus dilating effect (DADE) of lipo-PGE1 (a lipid emulsion preparation of prostaglandin E1 for injection) preparations. Lipo-PGE1 was administered intravenously via the umbilical vein by a bolus injection or an infusion in newborn rats 60 min after the delivery. The DADE data were expressed as the inner diameter ratio between the ductus arteriosus and the main pulmonary artery, and were analyzed by a pharmacological response kinetic (PRK) model consisting of an Emax model and a simple pharmacokinetic model as the pharmacodynamic- and the pharmacokinetic-component, respectively. The latter component includes the release process of free-PGE1 from the lipid phase of lipo-PGE1, followed by distribution to the effect compartment. The Emax value was estimated by the maximal DADE observed 10 min after the bolus administration of each dose, and the value was fixed in the PRK analysis. The regression curves given by simultaneous non-linear least squares regression analysis were satisfactorily fitted to the observed DADE data at all doses. Prediction of the DADE of lipo-PGE1 in an infusion study was satisfactorily done using the estimated parameters in the i.v.-study. These findings indicate that PRK modeling based on the intensities of the observed pharmacological response-time data is a meaningful tool in some targeting-type drugs, for which pharmacokinetic analysis itself is meaningless or acquisition of pharmacokinetic data is technically impossible, in predicting the time courses of the drug's pharmacological response in different dosage regimens.

Alprostadil↗
PubMed1984

Insulin responses to varying profiles of subcutaneous insulin infusion: kinetic modelling studies.

Refinement of continuous subcutaneous insulin infusion for diabetes therapy requires improved knowledge of subcutaneous insulin absorption kinetics. We have used kinetic modelling to quantitate systemic insulin delivery produced by subcutaneously-infused insulin (i.e. simulated meal and basal delivery). Profiles were studied in normal subjects, with endogenous insulin suppressed. Paired studies of intravenous insulin infusion enabled systemic insulin delivery to be quantitated. High rate subcutaneous delivery (10 U in 5 min) resulted in a systemic delivery of approximately 8 U in 4 h. Increasing infused insulin concentration delayed systemic delivery (p less than 0.025). Both continuous and pulsatile low-rate infusions (2.4 U/h) gave similar slow increases in systemic delivery to 1 U after 4 h. Computer fitting to a two-pool model of the subcutaneous space suggested a low rate of insulin degradation for all profiles (rate constant less than 10%/h). We conclude that: systemic insulin delivery following subcutaneous infusion conforms reasonably to a two-pool model, subcutaneous insulin degradation is low regardless of input profile, a long delay in basal systemic delivery should be taken into account when initiating or resuming interrupted subcutaneous insulin infusion. Kinetic modelling of subcutaneous insulin absorption should be useful to predict the impact of programming strategies for continuous subcutaneous insulin infusion therapy.

Adult↗
PubMed1989

Kinetic modeling of selenium metabolism in nonpregnant ewes.

The kinetics of selenium metabolism in three nonpregnant ewes were studied by the intravenous injection of 75Se-sodium selenite and measurement of radioactivity responses in blood, tissues and excreta. Stable selenium measurements were also made to determine selenium intake, excretion in feces and urine, and mass of selenium in tissues. Immediately following tracer injection, there was a rapid disappearance of radioactivity from plasma reflecting the uptake of the element by the liver and blood cells. The decrease in plasma radioactivity ceased abruptly by 30-45 min, and was followed by an increase to a peak by 3-4 h and a more gradual biphasic decline thereafter. A kinetic model of selenium metabolism in the whole animal was constructed employing the SAAM/CONSAM computer program. The multiphasic response of plasma radioactivity during a physiological steady state was explained on the basis of rapid hepatic uptake of selenium and its subsequent reappearance in the circulation in protein-bound form followed by further metabolism and excretion of the element. The model provides reference parameter values for 75Se-sodium selenite kinetics in selenium-replete, mature nonpregnant ewes for comparison with the kinetics in animals whose selenium status may be altered.

Animals↗
PubMed2006

Integrated chemical--physical processes kinetic modelling of multiple mineral precipitation problems.

A three-phase (aqueous/gas/solid) mixed weak acid/base chemistry kinetic model is applied to evaluate the processes operative in the aeration treatment of swine wastewater (SWW) and sewage sludge anaerobic digester liquor (ADL). In both applications, with a single set of constants (except for the aeration rates which are situation specific), close correlation could be obtained between predicted and measured data, except for the Ca concentration-time profile in the SWW. For this wastewater, the model application highlighted an inconsistency in the measured Ca data which could not be resolved; this illustrates the value of a mass balance-based model in evaluating experimental data. From the model applications, in both wastewaters the dominant minerals precipitating are struvite and amorphous calcium phosphate (ACP), which precipitate simultaneously competing for the same species, P. The absolute and relative masses of the two precipitants are governed by the initial solution state (e.g. total inorganic C (C(T)), Mg, Ca and P concentrations), their relative precipitation rates (struvite > ACP) and the system conditions imposed (aeration rates and time applied). It is concluded that the kinetic model is able to predict correctly the time-dependent weak acid/base chemistry reactions and final equilibrium state for situations where multiple minerals competing for the same species precipitate simultaneously or sequentially, a deficiency in traditional equilibrium chemistry-based algebraic models.

Aerobiosis↗
PubMed1990

Kinetic models for insulin disappearance from plasma in man.

The general use of first order kinetics to describe the disappearance of insulin from plasma in man contrasts the available evidence of saturation kinetics for insulin. In order to bridge this gap, we have put forward three alternative models of insulin kinetics. Model 1 considers the combined existence of first order and saturation (Michaëlis-Menten) kinetics. Model 2 considers saturation kinetics alone. Model 3 considers first order kinetics alone. The validity of the models was studied in normal and type I (insulin-dependent) diabetic subjects. Sequential constant intravenous infusions of insulin at different rates were used to achieve different levels of steady state plasma insulin concentrations, while the glycaemic level (usually normoglycaemia) was maintained by a glucose clamp. Appropriate validation procedures demonstrated that the model of saturation kinetics alone (model 2) was superior to the other models in normal subjects at physiological and supraphysiological plasma insulin concentrations, and in diabetic patients at supraphysiological concentrations. The minimal model at physiological insulin concentrations in type I diabetic patients was that of first order kinetics (model 3). The kinetics of insulin was independent of the species of insulin (human or porcine) in both study groups. The actual glycaemic clamp level (normoglycaemia and moderate hyperglycaemia) did not influence the insulin disappearance rate. Binding of insulin to its receptor is considered to be the initial step in insulin degradation. Saturation kinetics of insulin may therefore be influenced by the saturation of binding of insulin molecules to their receptors. We found values of Km (i.e. the concentration of plasma insulin at which the insulin disappearance rate is half maximal) in normal subjects comparable to values of Kd (i.e. the dissociation constant for insulin-receptor binding) from receptor studies in isolated cells. Changes in regional (hepatic and/or renal) blood flow at hyperinsulinaemia represent an alternative explanation to a model of saturation kinetics. Increases in Vmax (i.e. the maximal insulin disappearance rate) and Km with increasing insulin dose were observed in normal subjects. This finding suggests that insulin may disappear from plasma by more than one saturable pathway. Additional studies are needed to confirm this observation. The clearance rate of insulin at infinitesimal plasma insulin concentrations (Vmax/Km) was 28 +/- 8 ml.kg-1.min-1 in normal subjects. This value is higher than most clearance rates previously reported in studies using first order kinetics. The clearance rate of insulin in type I diabetic patients was 20 +/- 4 ml.kg-1.min-1, corresponding to a reduction in clearance of 30% compared to normal subjects.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗
PubMed2003

Development of expanded and core kinetic models for the gas phase formation of dioxins from chlorinated phenols.

Expanded, 45 reaction, and core, 12 reaction, kinetic models have been developed that account for the major features in the homogeneous formation of polychlorinated dibenzo-p-dioxins (PCDD) from the oxidation of 2,4,6-trichlorophenol (P). The expanded and core schemes provide good agreement between experimental and calculated yields of PCDDs using the CHEMKIN combustion package or the React kinetic program, respectively. Steady-state approximations of the reaction kinetic models including radical-molecule and radical-radical formation pathways of PCDD, as well as oxidative destruction pathways of chlorinated phenoxyl radicals, reveal a competition between reactions of chlorinated phenoxyl radicals with chlorinated phenols, recombination reactions of chlorinated phenoxyl mesomers, and destruction/decomposition of phenoxyl radicals.

Chlorophenols↗
PubMed1999

Ectoenzymatic Activity and Uptake of Monomers in Marine Bacterioplankton Described by a Biphasic Kinetic Model.

Abstract The kinetics of bacterial hydrolytic ectoenzymatic activity and the uptake of monomeric compounds were investigated in the Northwestern Mediterranean Sea. Aminopeptidase and alpha- and beta-glucosidase activities were analyzed by using fluorogenic substrates at 15-22 concentrations ranging from 1 nM to 500 µM. Radiolabeled glucose and a mixture of amino acids were chosen as representatives of monomeric compounds, and the bacterial uptake rates (assimilation plus respiration) were determined over a wide range of substrate concentrations (from 0.2 nM to 3 µM). We found biphasic kinetics both for hydrolytic enzymes and uptake systems: high affinity enzymes at low concentrations of substrates (Km values ranged from 48 nM to 2.7 µM for ectoenzymes and from 1.4 nM to 42 nM for uptake systems), and low affinity enzymes at high concentrations of substrates (Km values ranged from 18 µM to 142 µM for ectoenzymes and from 0.1 µM to 1.3 µM for uptake systems). Transition between high and low affinity enzymes was observed at 10 µM for aminopeptidase and from 1 µM to 25 µM for glucosidases, and it was more variable and less pronounced for the uptake of glucose (40 nM-0.28 µM) and amino acids (10 nM-0.16 µM). Results showed that the potential rates of hydrolysis and uptake are tightly coupled only if the high affinity hydrolytic ectoenzymes and the low affinity uptake systems are operating simultaneously.

Journal Article↗
PubMed2003

Kinetic modeling of TiO2-catalyzed photodegradation of trace levels of microcystin-LR.

A kinetic model has been developed to investigate the relative importance of major pathways for the photocatalytic degradation of trace levels of the cyanobacterial toxin microcystin-LR (MLR) in solutions containing a complex suite of dissolved organic matter and to test the sensitivity of MLR degradation to rate constants of the key processes. The kinetic model incorporates adsorption of the trace contaminant, other organics and oxygen on the particle surface, surface reactions between adsorbed radical and nonradical species, desorption of surface radical species, solution phase radical reactions, and radical termination pathways. Under conditions where the contaminant adsorbs strongly to semiconductor surface sites, rapid degradation is observed, and a primary degradation step appears to involve reaction between surface-located long-lived organic radicals (formed from hydroxyl radical scavenging by the bulk organic) and adsorbed trace contaminant. MLR degradation is relatively insensitive to changes in light intensity under these strongly adsorbing conditions but highly dependent under weakly adsorbing conditions and when solution phase degradation is important. While not verified independently, desorption of surface bound superoxide appears to lead to the production of organic peroxyl radicals through reaction of superoxide with the bulk organic. These solution phase organic peroxyl radicals are highly reactive and appear to be the primary source of trace contaminant degradation under conditions where the trace contaminant shows no observable adsorption and surface degradation is negligible. Under alkaline conditions, adsorption of carbonate onto the particle surface results in scavenging of surface hydroxyl radicals to form surface carbonate radicals that rapidly quench surface bound superoxide. This prevents organic peroxyl production, the primary agent of solution-phase trace contaminant degradation.

Adsorption↗
PubMedDate not supplied

Growth kinetic model that describes the inhibitory and lytic effects of phenol on Candida tropicalis yeast.

The object of this work was to carry out a kinetic study on the Candida tropicalis cell lysis and to obtain a kinetic model that would describe the inhibitory and lytic effects of phenol on the yeast growth. From the experiments, a model for the growth kinetic behavior of the yeast was evolved. The proposed model describes satisfactorily the inhibitory and lytic effects of phenol on yeast cultures. From the kinetic model constants, it was found that C. tropicalis showed high affinity and tolerance toward phenol. The overall growth yields decreased when the initial phenol concentration increased, and it may be due to an increased maintenance coefficient and to cell lysis.

Candida↗
PubMed2002

Pharmacodynamics of amoxicillin/clavulanic acid against Haemophilus influenzae in an in vitro kinetic model: a comparison of different dosage regimens including a pharmacokinetically enhanced formulation.

OBJECTIVE: To study the pharmacodynamics of amoxicillin/clavulanic acid against different strains of Haemophilus influenzae in an in vitro kinetic model. The concentrations used corresponded to human serum levels obtained after 875 mg amoxicillin/clavulanic acid given b.i.d., 500/125 mg amoxicillin/clavulanic acid given t.i.d. and those obtained with a pharmacokinetically enhanced formulation containing 1125/125 mg amoxicillin/clavulanic acid (immediate release) and 875 mg amoxicillin (sustained release) given b.i.d. METHODS: Bacteria at an initial inoculum of 106 colony-forming units (CFU)/mL were exposed to amoxicillin/clavulanic acid with an initial concentration of approximately 15/3 mg/L, 8/3 mg/L simulating the peak levels in humans achieved after a dose of 875/125 mg and 500/125 mg with a half-life of 1 h. In addition, experiments with a 2000/125 mg pharmacokinetically enhanced formulation of amoxicillin/clavulanic acid given b.i.d. were performed. A repeated dose was given at 12 h after the initial dose of 875/125 mg and the pharmacokinetically enhanced formulation or at 8 and 16 h after the dose of 500/125 mg. The experiments were performed in an in vitro kinetic model, which consists of a spinner flask with a filter membrane fitted in between the upper part and the bottom part in order to prevent bacterial dilution. The medium is removed from the culture flask, through the filter, at a constant rate with a pump. Repeated samples were taken at intervals of 1-2 h up to 24 h during the experiments for viable counting. One of the strains of H. influenzae was also exposed to a constant concentration corresponding to the peak serum levels obtained after a dose of 500/125 mg. RESULTS: The concentrations of amoxicillin in the in vitro kinetic model were as expected. At the end of the experiment (24 h), there was a tendency for a greater bactericidal effect with 500/125 mg t.i.d., as compared to 875/125 b.i.d., with differences in CFUs between the two dosing regimens of 2.6 log10 CFU for H. influenzae LH 2803 and 1.8 log10 CFU for the other clinical strains. However, these differences did not reach statistical significance (P = 0.075 and 0.10, respectively). A statistically significant higher bactericidal effect was seen in the experiments with the pharmacokinetically enhanced formulation in comparison with the b.i.d. regimen both at 8, 16 and 24 h and at 8 and 16 h with the t.i.d. regimen. With the new formulation, no regrowth was seen at 24 h, similar to the results obtained with a constant concentration. CONCLUSIONS: Neither of the standard dosing regimens of amoxicillin (875/125 mg b.i.d. or 500/125 mg) used in our study, in which the time that the free (non-protein-bound) concentration the MIC (T > MIC) exceeding was less than 50%, was sufficient to achieve a complete bactericidal effect during the first 24 h of treatment. However, a statistically significant difference in bactericidal activity was seen at 8, 16 and 24 h vs. the b.i.d. regimen and at 8 and 16 h vs. the t.i.d. regimen with the pharmacokinetically enhanced formulation. This formulation gave a longer T > MIC (73-79%) of amoxicillin even though the concentration of clavulanic acid was only detectable for 45% of the dosing interval, and complete killing of all strains was obtained after 24 h.

Amoxicillin↗
PubMed1987

Molecular kinetic modelling of associative learning.

Three molecular (enzyme) kinetic models have been designed that exhibit the basic properties of associative learning (classical conditioning). The enzyme systems are acted upon by an 'unconditioned' and a 'conditioned' ligand: temporally paired application of the two ligands leads to covalent enzyme modification, which serves as 'memory trace'. The behaviour of the systems has been investigated by computer simulation. Although the models are hypothetic, they do not contain biochemically inconceivable steps. The models demonstrate that already fairly simple molecular events may produce the phenomenology of associative learning.

Adenylyl Cyclases↗
PubMed1990

Kinetic model of 2-deoxyglucose metabolism using brain slices.

A six-compartment, nine-parameter kinetic model of 2-deoxyglucose (2DG) metabolism, which includes bidirectional tissue transport, phosphorylation, two-step dephosphorylation, phosphoisomerization, and conjugation to UDP and macromolecules, has been derived. Data for analysis were obtained from 540- and 1,000-microns-thick hippocampal and hypothalamic brain slices, which were incubated in buffer containing [14C]2DG, frozen, extracted with perchlorate, and separated on anion-exchange columns. Solutions of the equations of the model were fit to the data by means of nonlinear least-squares analysis. These studies suggest that dephosphorylation is adequately described by a single reaction so that the model reduces to eight parameters. The in vitro rate constants for transport, phosphorylation, and dephosphorylation are very similar to prior in vivo results. The phosphoisomerization rate constant is similar to dephosphorylation, so glycosylated macromolecules slowly accumulate and gradually assume larger relative importance as other compounds disappear more rapidly. Rate constants for 540-microns slices from hypothalamus and hippocampus are similar, while 1,000-microns slices have smaller tissue transport constants and larger phosphorylation constants. The rate equation for glucose utilization of this model is relatively insensitive to uncertainties regarding the rate constants. Including later metabolic components in kinetic models improves the calculations of glucose utilization with long isotope exposures.

Algorithms↗
PubMed1992

Factors affecting survival of hemodialysis patients utilizing urea kinetic modeling. A critical appraisal of shortening dialysis times.

The objective of this study was to analyze risk factors affecting mortality rates (MR) in hemodialysis patients undergoing shortened dialysis time who were regularly kinetically modeled. Over a 14-month period, 180 in-center hemodialysis patients, 54% male, 46% female, 57% Black, 39% Caucasian, and 4% Hispanic, treated with rapid high efficiency dialysis (RHED = 2-3 h, 3 times/week) and conventional dialysis (3-4 h, 3 times/week) were studied. Median patient age was 56.7 years (16-84 years) and dialysis care ranged from 6 months to 18 years (mean +/- SD = 4.0 +/- 4.2 years). The patients underwent monthly urea kinetic modeling. The dialysis prescription was based upon normalizing Kt/V between 0.8 and 1.2 and the protein catabolic rate (PCRn) between 0.9 and 1.1. Thirty-three percent of the patients received recombinant human erythropoietin (r-HuEPO). The effects of various covariates, including primary diagnosis, post/predialysis BUN ratios, creatinine, albumin, calcium, phosphate, cholesterol, hemoglobin, r-HuEPO, Kt/V, and PCRn were analyzed using analysis of variance, chi 2 and linear discriminant function (DF) statistical methods. Several significant factors emerged as influencing outcome. The DF analysis produced a highly statistically significant (p < 0.0001) model to predict mortality based upon certain laboratory and dialysis parameters. Further, the linear DF correctly predicted mortality rate in 86% of cases. The results of the analysis revealed an overall mortality rate of 15.6%; hospitalization rates (HR) were 1.4 +/- 1.8 times/year. Length of dialysis time, i.e., dialysis times between 2 and 4 h, when adjusted for Kt/V has no correlation with MR or HR. Variables associated with survival were higher post/predialysis BUN ratios, normal Kt/V (0.8-1.2), normal albumin levels (> 3.5 g/dl), higher postdialysis BUN, creatinine, and cholesterol levels, and use of r-HuEPO. The use of r-HuEPO when analyzed by DF significantly improved MR, 8.3% as opposed to 19.2%. It is concluded that urea kinetic modeling permits shortening dialysis times without affecting mortality or hospitalization rates, and that low postdialysis BUN, post/predialysis BUN ratios, creatinine, and albumin values are correlated with a lower chance of survival.

Analysis of Variance↗
PubMed1986

Two approaches to modeling kinetics of biodegradation by growing cells and application of a two-compartment model for mineralization kinetics in sewage.

The patterns of microbial mineralization of 0.3 to 30 ng of glucose, benzoate, and phenol per ml of sewage collected in late fall and winter were analyzed with the integrated Monod equation and a model in which growth of active organisms occurs at the expense of organic compounds other than the test substrate. Either model could be closely fit by nonlinear regression to the data from individual tests with one concentration of substrate added to one dilution of sewage. However, neither model accounted satisfactorily for differences in patterns of mineralization resulting from differences in substrate concentration and cell density between different tests. It is suggested that both the added substrates and other organics present in sewage contributed to the growth of the active organisms. The mineralization of glucose in sewage collected in summer was better described by a two-compartment model than by any other model tested.

Bacteria↗
PubMedDate not supplied

Peritoneal dialysis kinetic modeling: validation in a multicenter clinical study.

OBJECTIVE: To clinically validate the use of a computer-based kinetic model for peritoneal dialysis (PD) by assessing the level of agreement between measured and modeled values of urea and creatinine clearances and ultrafiltration (UF). DESIGN: An open multicenter observational study. PATIENTS: There were 111 adult continuous ambulatory peritoneal dialysis (CAPD) patients (47 female, 64 male) in four centers. All patients underwent a four-hour peritoneal equilibration test (PET) using 2.5% dextrose but with variable fill volumes (range: 1-3 L). Patients with a residual renal function greater than 10 mL/min were excluded. MAIN OUTCOME MEASURES: Correlations and limits of agreement between measured and modeled values of total weekly urea KT/V, total weekly normalized creatinine clearance (L/week/1.73 m2), daily drain volume (L), net ultrafiltration (L), daily peritoneal urea clearance (L/day), and daily peritoneal creatinine clearance (L/day). Measured values were obtained from 24-hour urine and dialysate collections while modeled values were based on results from the PET in combination with the PD ADEQUEST kinetic program. RESULTS: The results show there is excellent agreement between measured and modeled urea KT/V and creatinine clearances, with concordance correlations of 0.94 and 0.92, respectively. Given the excessive variation and limited range in ultrafiltration values, the concordance correlation between measured and modeled UF was only 0.50. In terms of daily peritoneal clearances and ultrafiltration, the level of precision (i.e., standard deviation) in the differences between modeled and measured values is +/- 1.05 L/day for urea clearance +/- 1.03 L/day for creatinine clearance, and +/- 0.919 L/day for ultrafiltration. By contrast, the level of precision (i.e., standard deviation) in the differences between two measured values is estimated to be +/- 0.979 L/day for urea clearance, +/- 0.802 L/day for creatinine clearance, and +/- 0.707 L/day for ultrafiltration. Defining the limits of clinical agreement to be +/- 2 standard deviations of the differences between two clinically measured 24-hour clearances (or ultrafiltration), we find that 94% of the modeled urea clearances, 87% of the modeled creatinine clearances, and 86% of the modeled ultrafiltration values fall within the limits of clinical agreement. CONCLUSION: Data for a carefully performed PET and overnight exchange can, in combination with a scientifically validated kinetic model, provide clinicians with a powerful mathematical tool for use in CAPD dialysis prescription management. Although not intended to replace actual measurements, kinetic modeling can prove useful as a means for predicting clearances for various alternative prescriptions and perhaps also as a means for checking certain types of noncompliance.

Adult↗
PubMed1996

Effect of intravascular ligand binding on parameter estimates derived from tracer kinetic modelling.

The purpose of this study was to assess the effect of intravascular ligand binding on parameter estimates derived from tracer kinetic modelling. To this end intravascular ligand kinetics between the free and a bound compartment in plasma and the exchange of tracer between the capillary space and tissue were analysed using a simple compartment model. The effect of non-equilibrated intravascular compartments on parameter estimates was evaluated in a computer simulation. It was found that three kinetic situations must be distinguished. If the intravascular compartments are fully equilibrated when the ligand reaches the target organ, intravascular binding simply acts as a scale factor for the transport-related parameter K1. If the intravascular kinetics is very slow, only minimal binding will occur. In between there is a range where ongoing equilibration leads to time variability of K1. Since tracer kinetic modelling usually does not account for such time variability, the parameter estimates become biased, the degree of the bias depending on the intravascular binding kinetics. Furthermore the bias may be dependent on receptor density, meaning that model-derived receptor estimates are not linearly related to the true receptor density. It is concluded that intravascular ligand binding can severely affect parameter estimates derived from tracer kinetic modelling. Especially disturbing are effects due to ongoing intravascular equilibration following the arrival of the ligand in the target organ. These can be avoided by letting the ligand equilibrate with blood in a syringe prior to injection.

Blood Vessels↗
PubMed1996

Kinetic model of molybdenum metabolism developed from dual stable isotope excretion in men consuming a low molybdenum diet.

The aim of this study was to develop a compartmental model of molybdenum metabolism based on stable isotope excretion patterns. Molybdenum (Mo) is an essential trace element in humans, with an estimated safe and adequate daily dietary intake (ESADDI) of 75-250 micrograms Mo/d. Four adult men were fed low molybdenum diets, 22 micrograms Mo/d for a period of 102 d. 97Mo+ and 100Mo stable isotopes, in intravenous and oral doses, respectively, were administered at selected intervals. The resulting 6-d cumulative urinary and fecal isotope excretion data were used to model molybdenum metabolism using SAAM/CONSAM software. A kinetic model, including gastrointestinal (GI), plasma, slow-turnover tissue and fast-turn-over tissue compartments, accurately simulated the observed pattern of urinary and fecal excretion for both stable isotopes in all four subjects. Residence time for molybdenum in the GI tract was estimated at 1.7 +/- 0.4 d. Predicted residence time for plasma molybdenum was 22 +/- 4 min, whereas slow-turnover tissue (possible hepatic) retention averaged 58 +/- 16 d. The model thus permitted estimation of kinetic parameters for molybdenum metabolism in tissues not readily accessible or measurable in humans.

Adult↗
PubMed1991

Accuracy of hemodialysis urea kinetic modeling. Comparison of different models.

To test the accuracy of urea kinetic modeling (UKM), the classic fixed-volume model UKMf, two variable-volume models (UKMvb and UKMvd), direct dialysis quantification (DDQ) and a partial dialysate collection method (PDC) were evaluated in 15 stable, high-hematocrit patients. Urea generation rate (G) was also determined from a 1-week collection of total dialysate and urine (OWC). The results, except distribution volumes, were highly correlated. However, Kt/V, the normalized whole-body urea clearance, was about 8% higher with UKMvb and UKMvd. Two of three simple equations for Kt/V rendered grossly deviating, but highly correlating, results. The normalized protein catabolic rate was 8% higher with UKMvd. With OWC as reference, UKMvb and UKMvd overestimated G by 19 and 15%, respectively. All results of PDC closely followed those of DDQ. This method may be an alternative for exact quantification. Before using a new UKM method it should be compared to an established reference method.

Adult↗