The Kinetics of Efflux of 5,5-Dimethyl-2,4-Oxazolidinedione (DMO) from the Myocardium

1976 ◽  
Vol 51 (2) ◽  
pp. 197-201
Author(s):  
P. A. Poole-Wilson
Keyword(s):  
Skeletal Muscle ◽  
Steady State ◽  
Rate Constants ◽  
Buffering Capacity ◽  
Distribution Volume ◽  
Steady State Distribution ◽  
State Distribution ◽  
Intracellular Compartments ◽  
Kinetics Of ◽  
Effluent Curve

1. The efflux of 14C-Iabelled 5,5-dimethyl-2,4-oxazolidinedione (DMO) from the myocardium of the rabbit has been studied. The perfusate pH was 7·38. 2. The effluent curve is complex and appears to be the resultant of movement between at least four compartments. 3. The first two probably represent intravascular and extracellular compartments; the last two have smaller rate constants and may represent intracellular spaces. Intracellular pH (pH1) calculated from the effluent curve was 7·23 ± 0·05. pH1 estimated from the steady-state distribution volume of DMO was 7·28 ± 0·02. 4. The existence of two intracellular compartments suggests that DMO is not homogeneously distributed in the myocardium. It is suggested that the apparent greater buffering capacity of cardiac than skeletal muscle can be explained by the greater number and volume of mitochondria in the myocardium, compartmentalization of DMO and assumptions inherent in the DMO method for the measurement of pH1.

Kinetic analysis of mechanism of intestinal Na+-dependent sugar transport

1985 ◽  
Vol 248 (5) ◽  
pp. C498-C509 ◽  
Author(s):  
D. Restrepo ◽  
G. A. Kimmich
Keyword(s):  
Experimental Data ◽  
Steady State ◽  
Sugar Transport ◽  
Enzyme Kinetic ◽  
Steady State Distribution ◽  
State Distribution ◽  
Least Squares Fit ◽  
Coupling Stoichiometry ◽  
Rate Limiting ◽  
Kinetics Of

Zero-trans kinetics of Na+-sugar cotransport were investigated. Sugar influx was measured at various sodium and sugar concentrations in K+-loaded cells treated with rotenone and valinomycin. Sugar influx follows Michaelis-Menten kinetics as a function of sugar concentration but not as a function of Na+ concentration. Nine models with 1:1 or 2:1 sodium:sugar stoichiometry were considered. The flux equations for these models were solved assuming steady-state distribution of carrier forms and that translocation across the membrane is rate limiting. Classical enzyme kinetic methods and a least-squares fit of flux equations to the experimental data were used to assess the fit of the different models. Four models can be discarded on this basis. Of the remaining models, we discard two on the basis of the trans sodium dependence and the coupling stoichiometry [G. A. Kimmich and J. Randles, Am. J. Physiol. 247 (Cell Physiol. 16): C74-C82, 1984]. The remaining models are terter ordered mechanisms with sodium debinding first at the trans side. If transfer across the membrane is rate limiting, the binding order can be determined to be sodium:sugar:sodium.

Remifentanil Versus Alfentanil

1996 ◽  
Vol 84 (4) ◽  
pp. 821-833. ◽  
Author(s):  
Talmage D. Egan ◽  
Charles F. Minto ◽  
David J. Hermann ◽  
Juliana Barr ◽  
Keith T. Muir ◽  
...  
Keyword(s):  
Steady State ◽  
Distribution Volume ◽  
Maximum Effect ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Maximal Effect ◽  
Steady State Distribution ◽  
State Distribution ◽  
Blood Concentrations ◽  
Arterial Blood

Background Remifentanil is an esterase-metabolized opioid with a rapid clearance. The aim of this study was to contrast the pharmacokinetics and pharmacodynamics of remifentanil and alfentanil in healthy, adult male volunteers. Methods Ten volunteers received infusions of remifentanil and alfentanil on separate study sessions using a randomized, open-label crossover design. Arterial blood samples were analyzed to determine drug blood concentrations. The electroencephalogram was employed as the measure of drug effect. The pharmacokinetics were characterized using a moment analysis, a nonlinear mixed effects model (NONMEM) population analysis, and context-sensitive half-time computer simulations. After processing the raw electroencephalogram to obtain the spectral edge parameter, the pharmacodynamics were characterized using an effect compartment, inhibitory maximum effect model. Results Pharmacokinetically, the two drugs are similar in terms of steady-state distribution volume (VD(SS)), but remifentanil's central clearance (CLc)) is substantially greater. The NONMEM analysis population pharmacokinetic parameters for remifentanil include a CLc of 2.9 l x min(-1), a VDss of 21.81, and a terminal half-life of 35.1 min. Corresponding NONMEM parameters for alfentanil are 0.36 l x min(-1), 34.11, and 94.5 min. Pharmacodynamically, the drugs are similar in terms of the time required for equilibration between blood and the effect-site concentrations, as evidenced by a T(12)k(e0) for remifentanil of 0.75 min [corrected] and 0.96 min for alfentanil. However, remifentanil is 19 times more potent than alfentanil, with an effective concentration for 50% maximal effect of 19.9 ng x ml(-1) versus 375.9 ng x ml(-1) for alfentanil. Conclusions Compared to alfentanil, the high clearance of remifentanil, combined with its small steady-state distribution volume, results in a rapid decline in blood concentration after termination of an infusion. With the exception of remifentanil's nearly 20-times greater potency (30-times if alfentanil partitioning between whole blood and plasma is considered), the drugs are pharmacodynamically similar.

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.

PROCESSOR SHARING G-QUEUES WITH INERT CUSTOMERS AND CATASTROPHES: A MODEL FOR SERVER AGING AND REJUVENATION

2017 ◽  
Vol 31 (4) ◽  
pp. 420-435 ◽  
Author(s):  
J.-M. Fourneau ◽  
Y. Ait El Majhoub
Keyword(s):  
Steady State ◽  
Product Form ◽  
Processor Sharing ◽  
Service Capacity ◽  
Steady State Distribution ◽  
State Distribution ◽  
Signal Arrival ◽  
Open Networks ◽  
Networks Of Queues

We consider open networks of queues with Processor-Sharing discipline and signals. The signals deletes all the customers present in the queues and vanish instantaneously. The customers may be usual customers or inert customers. Inert customers do not receive service but the servers still try to share the service capacity between all the customers (inert or usual). Thus a part of the service capacity is wasted. We prove that such a model has a product-form steady-state distribution when the signal arrival rates are positive.

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