1997
DOI: 10.1097/00000542-199710000-00024
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Computer Simulation of the Effects of Alterations in Blood Flows and Body Composition on Thiopental Pharmacokinetics in Humans 

Abstract: The physiological pharmacokinetic model developed in rats predicts thiopental pharmacokinetics in humans. Differences in basal cardiac output may explain much of the variability in early thiopental disposition between subjects.

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Cited by 92 publications
(57 citation statements)
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“…These analyses suggest that the heterogeneity of diffusion barriers may invalidate the simplistic assumption that tissue distribution clearances may be equated with blood flows. However, the limitations to thiopental diffusion into brain, heart, liver, and muscle were low in the report of Ebling et al (1994) and lower or even absent in their corrected model (Wada et al, 1997). Blood flow to these tissues accounted for 57% of cardiac output (Wada et al, 1997), which compares favorably with the 55% of cardiac output represented by thiopental distributive clearances in the present recirculatory model [i.e., (CL T-F ϩ CL T-S )/CL tot ] ( Table 2).…”
Section: Early Antipyrine and Thiopental Kinetics Do Not Differ 597mentioning
confidence: 89%
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“…These analyses suggest that the heterogeneity of diffusion barriers may invalidate the simplistic assumption that tissue distribution clearances may be equated with blood flows. However, the limitations to thiopental diffusion into brain, heart, liver, and muscle were low in the report of Ebling et al (1994) and lower or even absent in their corrected model (Wada et al, 1997). Blood flow to these tissues accounted for 57% of cardiac output (Wada et al, 1997), which compares favorably with the 55% of cardiac output represented by thiopental distributive clearances in the present recirculatory model [i.e., (CL T-F ϩ CL T-S )/CL tot ] ( Table 2).…”
Section: Early Antipyrine and Thiopental Kinetics Do Not Differ 597mentioning
confidence: 89%
“…The largest parenchymal diffusion barrier reported by Ebling et al (1994) and Wada et al (1997) was that of the skin. This corresponds to the observation of Renkin (1955) that blood flow to an isolated hindlimb equaled antipyrine distribution clearance only when the limb was skinned.…”
Section: Early Antipyrine and Thiopental Kinetics Do Not Differ 597mentioning
confidence: 94%
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“…If one calculates the organ mass-weighted average of thiopental tissue partition coefficients measured in 11 organs of the systemic circulation in rat (Ebling et al, 1994), one obtains a value of K p ϭ 1.35 that is well in accordance with our estimate of 1.49 Ϯ 0.19. Note that a comparison of tissue partition coefficients between rat and dog appears justified because the successful scaling up of thiopental pharmacokinetics from rat to human (Wada et al, 1997) suggests that tissue partition coefficients show little variation among species. The estimates of the model-independent parameters CL and V ss are not statistically significant different from those estimated previously with a different circulatory model (Avram et al, 2002).…”
Section: Discussionmentioning
confidence: 99%
“…These models can explain the effect of changes in cardiac output but do not account for the role of tissue partitioning and intratissue diffusion as determinants of systemic distribution kinetics of thiopental. Physiologically based models, in contrast, are very useful in explaining the effect of various physiological and anatomical factors on thiopental disposition using model simulation (Wada et al, 1997). However, they are far too complex to be fitted to plasma concentration-time data.…”
mentioning
confidence: 99%