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At least 541 records · Page 30Linked to original sources
PubMed1996

A model of the first pass passage of drugs from i.v. injection site to the heart--parameter estimates for lignocaine in the sheep.

A general model, based on indicator dilution principles, of the initial distribution and effects of drugs in a target organ after i.v. bolus administration is presented. The model was validated from previous studies of myocardial pharmacokinetics and pharmacodynamics of lignocaine in sheep. It is proposed that i.v. drug injection produces a concentration "peak" of drug in venous blood, which is attenuated by vascular mixing, and lung and heart kinetics, as the drug is transported from the injection site to the heart where it exerts its effects. The model predicted that the first passage of this peak through the heart was the principal component of myocardial concentrations of lignocaine for 10 min after injection before recirculation became important. Injection rate, cardiac output and myocardial blood flow were important determinants of the magnitude of the first pass peak. The model provides a physiological framework for analysing the initial distribution of drugs.

Anesthetics, Local↗
PubMed1993

In vitro evaluation of a continuous-sampling device for pharmacokinetic parameter estimation.

Using an in vitro pharmacokinetic model, area under the curve (AUC) estimates from an osmotic continuous-withdrawal device were compared to AUC estimates by a conventional trapezoidal method. Ten experiments were done under two different conditions: (a) half-life of 1 h (n = 5) and (b) half-life of 2 h (n = 5). Sampling was done for 6 and 12 h, respectively. The AUC estimates from the two methods were highly correlated (r = 0.948, p < 0.0001). The mean coefficient of variation was 9.5% (n = 10), and mean AUC values were not statistically different by analysis of variance (p = 0.4). The sampling device sampled at 0.121 +/- 0.011 ml/h; the mean volume was 0.79 +/- 0.03 and 1.34 +/- 0.02 ml over 6 and 12 h, respectively. Continuous sampling provided a reasonable estimation of AUC, required only one analytical sample, and sampled at a consistent zero-order rate.

Drug Monitoring↗
PubMed2005

Nonequilibrium model for estimating parameters of deleterious mutations.

Deleterious mutations are of extreme evolutionary importance because, even though they are eliminated by natural selection, their continuous pressure creates a pool of variability in natural populations. They are of potential relevance for the existence of several features in evolution, such as sexual reproduction, and pose a risk to small asexual populations. Despite their extreme importance, the deleterious mutation rate and the effects of each mutation on fitness are poorly known quantities. Here we analyze a simple model that can be applied to simple experiments, in microorganisms, aiming at the quantification of these values.

Adaptation, Physiological↗
PubMed1996

Optimized sampling and parameter estimation for quantification in whole body PET.

Whole-body positron emission tomography (PET) has recently emerged as an important imaging tool for cancer detection and staging. Initial applications of the technique have been primarily qualitative. One of the major reasons is the limits imposed by kinetically undersampled data over the whole body, as opposed to the standard method of continuous dynamic sampling in one body location. In this paper, a new estimation method using weighted nonlinear least squares (WNLS) for the first bed position and Bayesian regression (BR) for subsequent positions is proposed. A general criterion for designing optimal sampling schedules which maximizes the measurement information with multiple bed positions is developed. The overall approach is illustrated with the problem of estimating the metabolic rate of glucose (MRGLu) in tumors at different axial positions (image bed positions) in the body by using computer simulations and patient data. The results show that estimates of MRGLu using sparse data and the optimized Bayesian approach are comparable with those obtained by standard methods and fully sampled data. This study demonstrates the potential of the technique described for quantification where several bed positions have to be used to image all the regions of interest (ROI).

Abdominal Muscles↗
PubMed2000

Intersample fluctuations in phosphocreatine concentration determined by 31P-magnetic resonance spectroscopy and parameter estimation of metabolic responses to exercise in humans.

The ATP turnover rate during constant-load exercise is often estimated from the initial rate of change of phosphocreatine concentration ([PCr]) using 31P-magnetic resonance spectroscopy (MRS). However, the phase and amplitude characteristics of the sample-to-sample fluctuations can markedly influence this estimation (as well as that for the time constant (tau) of the [PCr] change) and confound its physiological interpretation especially for small amplitude responses. This influence was investigated in six healthy males who performed repeated constant-load quadriceps exercise of a moderate intensity in a whole-body MRS system. A transmit- receive surface coil was placed under the right quadriceps, allowing determination of intramuscular [PCr]; pulmonary oxygen uptake (VO2) was simultaneously determined, breath-by-breath, using a mass spectrometer and a turbine volume measuring module. The probability density functions (PDF) of [PCr] and VO2 fluctuations were determined for each test during the steady states of rest and exercise and the PDF was then fitted to a Gaussian function. The standard deviation of the [PCr] and VO2 fluctuations at rest and during exercise (sr and sw, respectively) and the peak centres of the distributions (xc(r) and xc(w)) were determined, as were the skewness (gamma1) and kurtosis (gamma2) coefficients. There was no difference between sr and sw for [PCr] relative to the resting control baseline (s(r) = 1.554 %delta (s.d. = 0.44), s(w) = 1.514 %delta (s.d. = 0.35)) or the PDF peak centres (xc(r) = -0.013 %delta (s.d. = 0.09), xc(w) -0.197 %delta (s.d. = 0.18)). The standard deviation and peak centre of the 'noise' in VO2 also did not vary between rest and exercise (sr = 0.0427 l min(-1) (s.d. = 0.0104), s(w) = 0.0640 l min(-1) (s.d. = 0.0292); xc(r) = -0.0051 l min(-1) (s.d. = 0.0069), xc(w) 0.0022 l min(-1) (s.d. = 0.0034)). Our results demonstrate that the intersample 'noise' associated with [PCr] determination by 31P-MRS may be characterised as a stochastic Gaussian process that is uncorrelated with work rate, as previously described for VO2. This 'noise' can significantly affect the estimation of tau[PCr] and especially the initial rate of change of [PCr], i.e. the fluctuations can lead to variations in estimation of the initial rate of change of [PCr] of more than twofold, if the inherent 'noise' is not accounted for. This 'error' may be significantly reduced in such cases if the initial rate of change is estimated from the time constant and amplitude of the response.

Adenosine Triphosphate↗
PubMed1995

Parameter estimation in six numerical models of transperitoneal transport of potassium in patients undergoing peritoneal dialysis.

The mechanisms of transperitoneal potassium transport during peritoneal dialysis were evaluated by validation of different mathematical models. The models were designed to elucidate the presence or absence of diffusive, non-lymphatic convective and lymphatic convective solute transport. Experimental results were obtained from 26 non-diabetic patients undergoing peritoneal dialysis. The validation procedure demonstrated that models including both diffusive and non-lymphatic convective solute transport were superior to the other models. Lymphatic convective solute transport was not identifiable. Furthermore, it was demonstrated experimentally that the equilibrium distribution of potassium between plasma water and dialysate did not differ from a Donnan equilibrium, although the precondition of the Donnan equilibrium was not fulfilled, i.e. the volumes on each side of the membrane were not constant and dialysate was not an ultrafiltrate of plasma.

Adult↗