Articles: biological-models.
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J Pharmacokinet Biopharm · Oct 1991
Comparative StudyA kinetic-dynamic model to explain the relationship between high potency and slow onset time for neuromuscular blocking drugs.
To account for experimental data showing increased onset time with increased potency of neuromuscular blocking drugs, a pharmacokinetic-pharmacodynamic model is presented. It is characterized by a finite concentration of receptors (R) in the effect compartment. Transfer from central to effect compartment is linearly related to concentration gradient. ⋯ The concentration of receptors in the effect compartment R which best fits experimental data obtained in humans is 0.28 mumol/L. With this value of R, onset times are prolonged when the ED95 (dose for 95% blockade) is less than 0.1 mumol/kg. It is concluded that, in the development of a short-acting nondepolarizing neuromuscular blocking drug, agents having an ED95 of 0.1 mumol/kg or greater appear more promising.
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A computer controlled infusion device for propofol was used to induce and maintain general anaesthesia in 20 children undergoing minor surgical procedures. The device was programmed with an adult pharmacokinetic model for propofol. During and after anaesthesia, blood samples were taken for measurement of propofol concentrations and it was found that the values obtained were systematically overpredicted by the delivery system algorithm. New pharmacokinetic microconstants were derived from our data which reflected more accurately the elimination and distribution of propofol in a prospective study involving another 10 children.
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The present work is a continuation of studies concerned with mathematical modelling and simulation of microvascular fluid and protein exchange following burn injuries [Bert et al.: Circulatory Shock 28: 199-219, 1989: Bowen et al.: Circulatory Shock 28: 221-233, 1989]. The model has been extended to include the effects of different types of fluid resuscitation on the circulatory and microvascular exchange systems. The model and a statistical fitting procedure were used to find the ranges of fitting parameter values that best describe the changes in interstitial fluid volume and protein mass as well as transcapillary protein extravasation for three sets of experiments (no resuscitation, resuscitation with Ringer's or resuscitation with plasma). Typical changes in mass exchange related parameters postburn that resulted in simulation predictions which were a good fit to the experimental data include: an increase in the large pore pathway for protein of 100 times in the injured skin and 5 times in non-injured skin and skeletal muscle, an increase in fluid filtration coefficients in injured skin of 10 times and an instantaneous decrease of 50% in the area available for exchange in injured skin at the time of the burn.
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IEEE Trans Biomed Eng · Jun 1991
A simple analytical solution to the three-compartment pharmacokinetic model suitable for computer-controlled infusion pumps.
The disposition of many drugs following an intravenous bolus injection can be described by a biexponential or triexponential equation. Computer-controlled infusion pumps have been developed which dose intravenous drugs based on models of drug disposition. These pumps can maintain steady plasma drug concentrations and facilitate controlled increases and decreases in drug concentration, enhancing titration of intravenous drugs. ⋯ Because of the complexity of these analytical solutions, other investigators have used numerical techniques to approximate the analytical solution. We have derived an extremely simple analytical solution to polyexponential disposition functions. This solution simplifies both the prediction of the plasma drug concentration by a computer-controlled infusion pump and the stepwise calculation of the infusion rate required to maintain constant plasma drug concentrations.