PubMed · 270913
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D L Costill. 1977. Sweating: its composition and effects on body fluids.. https://doi.org/10.1111/j.1749-6632.1977.tb38195.x
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One potential benefit of chronic hemodialysis (HD) regimens of longer duration or greater frequency than typical three-times-weekly schedules is enhanced solute removal over a relatively wide molecular weight spectrum of uremic toxins. This study assesses the effect of variations in HD frequency (F: per week), duration (T: min per treatment), and blood/dialysate flow rates (QB/QD: ml/min) on steady-state concentration profiles of five surrogates: urea (U), creatinine (Cr), vancomycin (V), inulin (I), and beta2-microglobulin (beta2M). The regimens assessed for an anephric 70-kg patient were: A (standard): F = 3, T = 240, QB = 350, QD = 600; B (daily/short-time): F = 7, T = 100, QB = 350, QD = 600; C/D/E (low-flow/long-time): F = 3/5/7, T = 480, QB = 300, QD = 100. HD was simulated with a variable-volume double-pool model, which was solved by numerical integration (Runge-Kutta method). Endogenous generation rates (G) for U, Cr, and beta2M were 6.25, 1.0, and 0.17 mg/min, respectively; constant infusion rates for V and I of 0.2 and 0.3 mg/min, respectively, were used to simulate middle molecule (MM) G values. Intercompartment clearances of 600, 275, 125, 90, and 40 ml/min were used for U, Cr, V, I, and beta2M, respectively, For each solute/regimen combination, the equivalent renal clearance (EKR: ml/min) was calculated as a dimensionless value normalized to the regimen A EKR, which was 13.4, 10.8, 6.6, 3.7, and 4.8 ml/min for U, Cr, V, I, and beta2M, respectively. For regimens B, C, D, and E, respectively, these normalized EKR values were U: 1.04, 0.96, 1.58, and 2.22; Cr: 1.03, 1.08, 1.80, and 2.55; V: 1.06, 1.32, 2.21, and 3.12; I: 1.05, 1.54, 2.57, and 3.62; beta2M: 1.00, 1.27, 1.73, and 2.19. The extent of post-HD rebound (%) was highest for regimens A and B, ranging from 16% (urea) to 50% (inulin), and lowest for regimen E, ranging from 6% (urea) to 28% (beta2M). The following conclusions can be made: (1) Relative to a standard three-times-weekly HD regimen of approximately the same total (weekly) treatment duration, a daily/short-time regimen results in modest (3 to 6%) increases in effective small solute and MM removal. (2) Relative to a standard three-times-weekly HD regimen, a three-times-weekly low-flow/long-time regimen results in comparable effective small solute removal and progressive increases in MM and beta2M removal. A daily low-flow/long-time regimen substantially increases the effective removal of all solutes.
After administration and absorption, some drugs can be excreted via various mechanisms from blood into the gut; the determination of this drug excretion rate may have important clinical and pharmaceutical implications. A three-compartment closed model with first-order absorption was designed using absorption, blood and eliminated compartments to estimate the drug transfer rate from blood into the gut. Theoretically, the excretion rates of drugs whose blood concentrations can be described by the one-compartment open model with first-order absorption can be estimated using the developed model. This theoretical deduction was supported by 100 Monte Carlo simulations performed in the present study. A sensitivity analysis suggests that the estimated drug transfer rate from blood into gut is very sensitive to blood drug concentrations. Meanwhile, an example also shows the limitation of the developed model.
Blood has been considered as a simplified tissue model, both physiologically and physically consisting in two compartments, extra-cellular and intra-cellular. In the physiologic condition (300 mOsm), the relaxation rates of red cell suspensions in saline increased linearly with the hematocrit in the range 0-0.80 according to Fullerton's model of fast proton exchanges between the two compartments (Fullerton GD, Potter JL, Dornbluth NC. NMR relaxation of protons in tissues and other macromolecular water solutions. Magn Reson Imaging 1982; 1:209-228). In experiments of osmotic variations, between 200 and 900 mOsm at three constant red cell numbers in the samples, non-linear variations of relaxation rates with red cell volume were observed. In the hyperosmotic domain, the particularly high increase in blood transverse relaxation rate with the decreasing cell volume has been attributed to the progressive water-protein organization in the cellular compartment. A generalised form of the fast exchange model has been applied to extended experimental conditions of red cells, by introducing the red cell volume ratio of modified to iso-osmotic values, and the volume fraction of iso-osmotic red cells.