Determination of Volume of Distribution at Steady State with Complete Consideration of the Kinetics of Protein and Tissue Binding in Linear Pharmacokinetics

2004 ◽  
Vol 93 (2) ◽  
pp. 364-374 ◽  
Author(s):  
Leonid M. Berezhkovskiy
Keyword(s):  
Steady State ◽  
Volume Of Distribution ◽  
Tissue Binding ◽  
Linear Pharmacokinetics ◽  
Kinetics Of

scholarly journals Determination of the steady-state turnover rates of the metabolically active pools of phosphatidylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate in human erythrocytes

1989 ◽  
Vol 259 (3) ◽  
pp. 893-896 ◽  
Author(s):  
C E King ◽  
P T Hawkins ◽  
L R Stephens ◽  
R H Michell
Keyword(s):  
Steady State ◽  
Rate Constants ◽  
Human Erythrocytes ◽  
Turnover Rates ◽  
Metabolic Fluxes ◽  
Metabolic Pool ◽  
Phosphatidylinositol 4 ◽  
Kinetics Of ◽  
Phosphate Groups

When intact human erythrocytes are incubated at metabolic steady state in a chloride-free medium containing [32P]Pi, there is rapid labelling of the gamma-phosphate of ATP, followed by a slower labelling of the monoester phosphate groups of phosphatidylinositol 4-phosphate (PtdIns4P) and phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] [King, Stephens, Hawkins, Guy & Michell (1987) Biochem. J. 244, 209-217]. We have analysed the early kinetics of the labelling of these phosphate groups, in order to determine: (a) the steady-state rates of the interconversions of phosphatidylinositol, PtdIns4P and PtdIns(4,5)P2; and (b) the fractions of the total cellular complement of PtdIns4P and PtdIns(4,5)P2 that participate in this steady-state turnover. The experimental data most closely fit a pattern of PtdIns4P and PtdIns(4,5)P2 turnover in which one-quarter of the total cellular complement of each lipid is in the metabolic pool that participates in rapid metabolic turnover, with rate constants of 0.028 min-1 for the interconversion of PtdIns and PtdIns4P, and of 0.010 min-1 for the PtdIns4P/PtdIns(4,5)P2 cycle. These rate constants represent metabolic fluxes of approx. 2.1 nmol of lipid/h per ml of packed erythrocytes between PtdIns and PtdIns4P and of approx. 5.7 nmol/h per ml of cells between PtdIns4P and PtdIns(4,5)P2.

Measurement of leucine metabolism in man from a primed, continuous infusion of L-[1-3C]leucine

1980 ◽  
Vol 238 (5) ◽  
pp. E473-E479 ◽  
Author(s):  
D. E. Matthews ◽  
K. J. Motil ◽  
D. K. Rohrbaugh ◽  
J. F. Burke ◽  
V. R. Young ◽  
...  
Keyword(s):  
Steady State ◽  
Continuous Infusion ◽  
Co2 Production ◽  
Human Beings ◽  
Priming Dose ◽  
Leucine Metabolism ◽  
Kinetics Of ◽  
13Co2 Enrichment

Leucine metabolism in vivo can be determined from a primed, continuous infusion of L-[1-13C]leucine by measuring, at isotopic steady state, plasm [-13C]leucine enrichment, expired 13CO2 enrichment, and CO2 production rate. With an appropriate priming dose of L-[1-13C]leucine and NaH13CO3, isotopic steady state is reached in less than 2 h, and the infusion is completed in 4 h. The method can determine rates of leucine turnover, oxidation, and incorporation into protein with typical relative uncertainties of 2, 10, and 4%, respectively. The method requires no more than 1 ml of blood and uses stable isotope rather than radioisotope techniques. Thus, the method is applicable to studies of human beings of all ages. L-[1-13C]leucine may be infused with a second amino acid labeled with 15N for simultaneous determination of the kinetics of two amino acids.

Noncompartmental Determination of the Steady‐State Volume of Distribution

1979 ◽  
Vol 68 (8) ◽  
pp. 1071-1074 ◽  
Author(s):  
Leslie Z. Benet ◽  
Renato L. Galeazzi
Keyword(s):  
Steady State ◽  
Volume Of Distribution

Distribution and kinetics of glucose in rats analyzed by noncompartmental and compartmental analysis

1990 ◽  
Vol 259 (2) ◽  
pp. E292-E303 ◽  
Author(s):  
M. Raman ◽  
J. Radziuk ◽  
G. Hetenyi
Keyword(s):  
Steady State ◽  
Rate Constant ◽  
Insulin Infusion ◽  
Compartmental Analysis ◽  
Volume Of Distribution ◽  
Turnover Rates ◽  
Glucose Release ◽  
Steady State Kinetics ◽  
Induced Changes ◽  
Kinetics Of

The steady-state kinetics and distribution of glucose were assessed using noncompartmental and various two-compartment models in rats that were infused with insulin (+/- euglycemic clamping), methylprednisolone (MP), or phlorizin (PHL) as well as rats injected with protamine-zinc-insulin (PZI) or rendered diabetic. Decreases in clearance of glucose (PCR) were greatest with insulin infusion, followed by PHL, MP, and PZI treatments. PCR decreased in diabetes to 25% of normal. With hyperinsulinemia and euglycemia, turnover rates were 1.18 times the rate of glucose infusion. In normal rats the ratio of the contents of the two compartments was 0.6-0.8 (depending on the model). Significant increases, of between 2.8 and 5.2, were observed with insulin infusion and between 0.8 and 1.8 with PHL, again depending on the model. Because PHL-induced changes in PCR are renal, these data suggest that variations in glucose distribution depend on changes in PCR as well as insulin. The intercompartmental rate constant decreased, and the noncompartmental volume of distribution increased to reflect the above changes. In non-steady-state studies, glucose release increased in response to insulin but not to PHL in contrast to other species.

scholarly journals Determination of Extracellular Space in Amphibian Muscle

1967 ◽  
Vol 50 (5) ◽  
pp. 1459-1465 ◽  
Author(s):  
Emil Bozler
Keyword(s):  
Connective Tissue ◽  
Volume Of Distribution ◽  
Slow Phase ◽  
Extracellular Water ◽  
Total Water ◽  
Related Substances ◽  
Inulin Space ◽  
Kinetics Of ◽  
Volumes Of Distribution

The volumes of distribution of inulin and dextran in the sartorius, stomach, and cardiac muscle of the frog agree rather closely. That these spaces represent the volume of extracellular water is supported by the observation that efflux of sucrose can be divided into a fast and a slow phase and that the fast-moving fraction corresponds closely with inulin space determined in the same muscle. These and other findings confirm that sugars and related substances penetrate slowly into part of the fiber water and that, therefore, their volume of distribution does not accurately represent the volume of extracellular water. The kinetics of efflux of sucrose is consistent with the assumption that the movement of sugars is determined by the resistance of the cell surface as well as by internal diffusion. In connective tissue, sucrose and inulin are excluded only from a small part of the total water.

Method for the determination of the arteriovenous muscle protein balance during non-steady-state blood and muscle amino acid concentrations

2005 ◽  
Vol 289 (6) ◽  
pp. E1064-E1070 ◽  
Author(s):  
Christos S. Katsanos ◽  
David L. Chinkes ◽  
Melinda Sheffield-Moore ◽  
Asle Aarsland ◽  
Hisamine Kobayashi ◽  
...  
Keyword(s):  
Steady State ◽  
Amino Acid ◽  
Muscle Protein ◽  
Volume Of Distribution ◽  
Protein Balance ◽  
Nonsteady State ◽  
Balance Technique ◽  
Amino Acid Concentrations ◽  
Rate Of Accumulation

We describe a method based on the traditional arteriovenous balance technique in conjunction with muscle biopsies for the determination of leg muscle protein balance during the nonsteady state in blood amino acid concentrations. Six young, healthy individuals were studied in the postabsorptive state (pre-Phe) and after a bolus ingestion of ∼0.5 g phenylalanine (post-Phe). Post-Phe free phenylalanine concentrations in blood and muscle increased ( P < 0.05), but the respective concentrations of the amino acid threonine did not change. The average post-Phe leg net balance (NB) for threonine decreased from basal ( P < 0.05), but that for phenylalanine did not change. A volume of distribution for free phenylalanine in the leg was calculated based on the leg lean mass and the relative muscle water content and used to estimate the rate of accumulation of free phenylalanine in the leg. When the post-Phe NB for phenylalanine was corrected for the rate of accumulation of free phenylalanine in the leg, the post-Phe NB for phenylalanine decreased from basal ( P < 0.05). This corrected value was not different ( P > 0.05) from the value predicted for the phenylalanine NB based on the pre- and post-Phe NB responses for threonine. We conclude that the protein NB in non-steady-state blood phenylalanine concentrations can be determined from the arteriovenous phenylalanine NB by accounting for changes in free phenylalanine within its volume of distribution.

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