scholarly journals The design of experiments using isotopes for the determination of the rates of disposal of blood-borne substrates in vivo with special reference to glucose, ketone bodies, free fatty acids and proteins

1973 ◽  
Vol 136 (3) ◽  
pp. 503-518 ◽  
Author(s):  
Dennis F. Heath ◽  
Roger N. Barton
Keyword(s):  
Fatty Acids ◽  
Steady State ◽  
Free Fatty Acids ◽  
Ketone Bodies ◽  
Specific Radioactivity ◽  
Constant Infusion ◽  
Time Curve ◽  
Constant Rate

1. The two well-known methods of estimating rates of irreversible disposal (R) of blood-borne substrates in vivo by isotope experiments involve estimating the specific radioactivity (S) of the substrate in blood either after single intravenous injection of labelled substrate or during its infusion at a constant rate. The value of R is calculated from the S–time curve, usually by assuming: (i) a metabolic steady state with respect to substrate, (ii) the passage of all substrate through the blood, and (iii) the absence of certain types of recycling via blood. 2. In a theoretical investigation we show how experiments can be performed and R calculated from analyses of blood when one or more of the above assumptions is unjustified, by using glucose, ketone bodies, plasma free fatty acids and proteins as examples. In general the methods require single injection procedures, with estimation of the total quantity of label in the substrate in blood and the substrate concentration instead of only S. Such values give estimates of R with standard errors even when only one blood specimen is taken from each of a group of animals, as is convenient when working with small animals or substrates in low concentration, and when the animals are in a non-steady state in which constant infusion procedures are invalid. 3. Similar methods give the fraction of label injected as one compound which passes through another (the isotopic yield). 4. The methods are not always applicable, and cannot be applied to plasma proteins in some pathological conditions. A questionnaire for assessing their applicability is given.

scholarly journals Tissue Penetration and Pharmacokinetics of Tigecycline in Diabetic Patients with Chronic Wound Infections Described by Using In Vivo Microdialysis

2010 ◽  
Vol 54 (12) ◽  
pp. 5209-5213 ◽  
Author(s):  
Catharine C. Bulik ◽  
Dora E. Wiskirchen ◽  
Ashley Shepard ◽  
Christina A. Sutherland ◽  
Joseph L. Kuti ◽  
...  
Keyword(s):  
Steady State ◽  
Protein Binding ◽  
Subcutaneous Tissue ◽  
Diabetic Patients ◽  
Tissue Penetration ◽  
Tissue Concentrations ◽  
Time Curve ◽  
The Mean

ABSTRACT Tissue penetration of systemic antibiotics is an important consideration for positive outcomes in diabetic patients. Herein we describe the exposure profile and penetration of tigecycline in the interstitial fluid of wound margins versus that of uninfected thigh tissue in 8 adult diabetic patients intravenously (IV) administered 100 mg and then 50 mg of tigecycline twice daily for 3 to 5 doses. Prior to administration of the first dose, 2 microdialysis catheters were inserted into the subcutaneous tissue, the first within 10 cm of the wound margin and the second in the thigh of the same extremity. Samples for determination of plasma and tissue concentrations were simultaneously collected over 12 h under steady-state conditions. Tissue concentrations were corrected for percent in vivo recovery by the retrodialysis technique. Plasma samples were also collected for determination of protein binding at 1, 6, and 12 h postdose for each patient. Protein binding data were corrected using a fitted polynomial equation. The mean patient weight was 95.1 kg (range, 63.6 to 149.2 kg), the mean patient age was 63.5 ± 9.4 years, and 75% of the patients were males. The mean values for the plasma, thigh, and wound free area under the concentration-time curve from 0 to 24 h (fAUC0-24) were 2.65 ± 0.33, 2.52 ± 1.15, and 2.60 ± 1.02 μg·h/ml, respectively. Protein binding was nonlinear, with the percentage of free drug increasing with decreasing serum concentrations. Exposure values for thigh tissue and wound tissue were similar (P = 0.986). Mean steady-state tissue concentrations for the thigh and wound were similar at 0.12 ± 0.02 μg/ml, and clearance from the tissues appeared similar to that from plasma. Tissue penetration ratios (tissue fAUC/plasma fAUC) were 99% in the thigh and 100% in the wound (P = 0.964). Tigecycline penetrated equally well into wound and uninfected tissue of the same extremity.

The reliability of rates of glucose appearance in vivo calculated from single tracer injections

1979 ◽  
Vol 57 (11) ◽  
pp. 1267-1274 ◽  
Author(s):  
John R. Allsop ◽  
Robert R. Wolfe ◽  
Joseph J. DiStephano III ◽  
John F. Burke
Keyword(s):  
Plasma Glucose ◽  
Infusion Rate ◽  
Specific Radioactivity ◽  
Glucose Production ◽  
Endogenous Glucose Production ◽  
Constant Infusion ◽  
Glucose Turnover ◽  
Time Curve ◽  
The Mean

The rate of appearance of unlabelled glucose was calculated from changes in plasma glucose specific radioactivity after a single intravenous injection of labelled glucose and compared with the actual constant infusion rate of unlabelled glucose into an anaesthetized dog with all sources of endogenous glucose production surgically removed. The mean steady-state rate of appearance of unlabelled glucose calculated from the area under the specific radioactivity versus time curve was 7% higher than the actual infusion rate (n = 4), but the difference was not statistically significant. The variability in the rate calculated in this manner was, however, greater than the variability we have reported with rates determined from a primed constant infusion of tracer. Using 15- to 60- or 60- to 120-min specific radioactivity data the mean rate of appearance of glucose, calculated on the assumption of a one-pool model for glucose turnover in vivo, was approximately 60% higher than the actual infusion rate. The results also indicate that it is possible to construct multi-pool models, but it is difficult to equate specific physiological events with the individual terms of the multi-exponential equation which describes the changes in plasma glucose specific radioactivity.

Resistance to Outflow of Cerebrospinal Fluid Determined by Bolus Injection Technique and Constant Rate Steady State Infusion in Humans

Neurosurgery ◽  
1985 ◽  
Vol 16 (3) ◽  
pp. 336-340 ◽  
Author(s):  
Michael Kosteljanetz
Keyword(s):  
Cerebrospinal Fluid ◽  
Steady State ◽  
Bolus Injection ◽  
Point Of View ◽  
Injection Technique ◽  
Communicating Hydrocephalus ◽  
Constant Rate ◽  
High Degree ◽  
Infusion Technique

Abstract Two methods for the determination of resistance to the outflow of cerebrospinal fluid, the bolus injection technique and the constant rate steady state infusion technique, were compared. Thirty-two patients with a variety of intracranial diseases (usually communicating hydrocephalus) were studied. There was a high degree of correlation between the resistance values obtained with the two methods, but values based on the bolus injection technique were systematically and statistically significantly lower than those obtained with the constant rate infusion test. From a practical point of view. both methods were found to be applicable in a clinical setting.

Effect of free fatty acids and detergents on H,K-ATPase. The steady-state ATP phosphorylation level and the orientation of the enzyme in membrane preparations

1991 ◽  
Vol 1070 (2) ◽  
pp. 283-292 ◽  
Author(s):  
Herman G.P. Swarts ◽  
Tom J.F. Van Uem ◽  
Sjouke Hoving ◽  
Jack A.M. Fransen ◽  
Jan Joep H.H.M. De Pont
Keyword(s):  
Fatty Acids ◽  
Steady State ◽  
Free Fatty Acids ◽  
Phosphorylation Level
Sign in / Sign up

Export Citation Format

Share Document