PubMed · 2473531
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J Ruiz, V Danel. 1989. [Volume expanders. Colloidal plasma substitutes].. https://pubmed.ncbi.nlm.nih.gov/2473531/
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The hypothesis that increased muscle T2 after exercise is caused by increased extracellular fluid volume was tested by comparing the effects of exercise versus external leg negative pressure on muscle T2 relaxation in normal human subjects. T2 in lower leg muscles was measured by echo-planar imaging at 63 echo times from 24 to 272 ms, and the relaxation spectrum was calculated by using a non-negative least squares algorithm. T2 relaxation in anterior leg muscle before exercise was characterized by a single component with mean T2 = 29.3 +/- 0.7 (SE, n = 5). After ankle dorsiflexion exercise, this single component broadened, and mean T2 increased to 38.3 +/- 0.7 ms. In contrast, after leg negative pressure, which increased the total leg muscle cross-sectional area by 21% (range 12-32% n = 6), there was a variable appearance of much slower-relaxing components (60-500 ms). The results suggest that increased extracellular fluid can account for only a minor portion of the increase in muscle T2 observed during exercise.
The presence of a biophase compartment in a pharmacokinetic model indicates that the response to an administered dose of drug is damped such that the time to peak effect occurs after the peak concentration in the bloodstream. This phenomenon, which is common to most intravenous anesthetic agents, can be exploited by a drug delivery method that administers minibolus doses of drug rather than a continuous infusion. Through analysis of the frequency response behavior of the biophase compartment, a bolus magnitude and dose frequency or interval (1/frequency) can be chosen such that the oscillation in drug effect is minimized even though the plasma concentration may be changing significantly with each supplemental dose. A pharmacokinetic and pharmacodynamic based method for calculating the bolus dose size and dosing interval is presented. The trade-off between dose interval and change in drug effect is exemplified through computer simulation of this strategy applied to delivery of the neuromuscular blocking agent pancuronium. The method provides a repetitive perturbation to the pharmacokinetic and pharmacodynamic system that can aid in model parameter identification during closed loop applications.
In conventional pharmacokinetics monotonic decreasing drug disposition curves are usually assumed after bolus injection. For arterial sampling starting about 1 min after dosing the resulting neglect of the initial concentration peak leads to a relative overestimation of clearance which may be approximated by the percentage of systemic drug extraction. This error can be avoided by administering the drug as a short-term infusion.