Application of the double-marker method for measuring digesta kinetics to rumen sampling in sheep following a dose of the markers or the end of their continuous infusion

1992 ◽  
Vol 43 (2) ◽  
pp. 277 ◽  
Author(s):  
GJ Faichney
Keyword(s):  
Single Dose ◽  
Steady State ◽  
Continuous Infusion ◽  
Equilibrium Phase ◽  
Fluid Phase ◽  
Particle Phase

Methods are described by which the double-marker method for measuring digesta kinetics may be applied to rumen samples taken from sheep maintained in steady-state conditions, while marker concentrations are declining after a single dose of the two markers, or cessation of their continuous infusion, or increasing in the pre-equilibrium phase of their unprimed continuous infusion. Also described are procedures for checking the consistency of analyses applied to digesta, fluid-phase and particle-phase samples and for physically reconstituting true digesta samples. Errors due to deviations of the markers from ideal behaviour are examined.

Single-Dose and Steady-State Pharmacokinetics of Diltiazem Administered in Two Different Tablet Formulations

1992 ◽  
Vol 71 (4) ◽  
pp. 305-307 ◽  
Author(s):  
Lona L. Christrup ◽  
Jan Bonde ◽  
Søren N. Rasmussen ◽  
Jørn Møller Sonnergaard ◽  
Bodil H. Jensen
Keyword(s):  
Single Dose ◽  
Steady State ◽  
Tablet Formulations

scholarly journals Phorbol esters and horseradish peroxidase stimulate pinocytosis and redirect the flow of pinocytosed fluid in macrophages.

1985 ◽  
Vol 100 (3) ◽  
pp. 851-859 ◽  
Author(s):  
J A Swanson ◽  
B D Yirinec ◽  
S C Silverstein
Keyword(s):  
Steady State ◽  
Horseradish Peroxidase ◽  
Phorbol Esters ◽  
Lucifer Yellow ◽  
Fluid Phase ◽  
Peritoneal Macrophages ◽  
Tumor Promoter ◽  
Steady State Rate ◽  
Reduced Rate ◽  
Rate Of Accumulation

Lucifer Yellow CH (LY) is an excellent probe for fluid-phase pinocytosis. It accumulates within the macrophage vacuolar system, is not degraded, and is not toxic at concentrations of 6.0 mg/ml. Its uptake is inhibited at 0 degree C. Thioglycollate-elicited mouse peritoneal macrophages were found to exhibit curvilinear uptake kinetics of LY. Upon addition of LY to the medium, there was a brief period of very rapid cellular accumulation of the dye (1,400 ng of LY/mg protein per h at 1 mg/ml LY). This rate of accumulation most closely approximates the rate of fluid influx by pinocytosis. Within 60 min, the rate of LY accumulation slowed to a steady-state rate of 250 ng/mg protein per h which then continued for up to 18 h. Pulse-chase experiments revealed that the reduced rate of accumulation under steady-state conditions was due to efflux of LY. Only 20% of LY taken into the cells was retained; the remainder was released back into the medium. Efflux has two components, rapid and slow; each can be characterized kinetically as a first-order reaction. The kinetics are similar to those described by Besterman et al. (Besterman, J. M., J. A. Airhart, R. C. Woodworth, and R. B. Low, 1981, J. Cell Biol. 91:716-727) who interpret fluid-phase pinocytosis as involving at least two compartments, one small, rapidly turning over compartment and another apparently larger one which fills and empties slowly. To search for processes that control intracellular fluid traffic, we studied pinocytosis after treatment of macrophages with horseradish peroxidase (HRP) or with the tumor promoter phorbol myristate acetate (PMA). HRP, often used as a marker for fluid-phase pinocytosis, was observed to stimulate the rate of LY accumulation in macrophages. PMA caused an immediate four- to sevenfold increase in the rate of LY accumulation. Both HRP and PMA increased LY accumulation by stimulating influx and reducing the percentage of internalized fluid that is rapidly recycled. A greater proportion of endocytosed fluid passes into the slowly emptying compartment (presumed lysosomes). These experiments demonstrate that because of the considerable efflux by cells, measurement of marker accumulation inaccurately estimates the rate of fluid pinocytosis. Moreover, pinocytic flow of water and solutes through cytoplasm is subject to regulation at points beyond the formation of pinosomes.

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.

Comparison of Fluconazole Pharmacokinetics in Serum, Aqueous Humor, Vitreous Humor, and Cerebrospinal Fluid Following a Single Dose and at Steady State

1998 ◽  
Vol 14 (5) ◽  
pp. 459-471 ◽  
Author(s):  
UMAR K. MIAN ◽  
MARTIN MAYERS ◽  
YOGENDER GARG ◽  
QING-FENG LIU ◽  
GIRARD NEWCOMER ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Single Dose ◽  
Steady State ◽  
Aqueous Humor ◽  
Vitreous Humor

scholarly journals Clinical Pharmacokinetics of Fosfomycin after Continuous Infusion Compared with Intermittent Infusion: a Randomized Crossover Study in Healthy Volunteers

2020 ◽  
Vol 65 (1) ◽  
pp. e01375-20
Author(s):  
Valentin al Jalali ◽  
Peter Matzneller ◽  
Beatrix Wulkersdorfer ◽  
Scharon Chou ◽  
Soma Bahmany ◽  
...  
Keyword(s):  
Steady State ◽  
Crossover Study ◽  
Healthy Volunteers ◽  
Continuous Infusion ◽  
Intermittent Infusion ◽  
Time Curve ◽  
Clinical Pharmacokinetics ◽  
Clinical Scenarios ◽  
Ringer’S Lactate ◽  
State Concentration

ABSTRACTContinuous infusion (CON) of fosfomycin has been proposed as potentially advantageous in certain clinical scenarios. However, no clinical data on the pharmacokinetics (PK) of fosfomycin after CON are available to date. This study aimed to investigate the PK of fosfomycin after CON and compare it with intermittent infusion (INT) of fosfomycin. A randomized two-way crossover study including 8 healthy male volunteers was performed. Each subject received fosfomycin as INT of 8 g over 30 min every 8 h and, separated by a washout period, as CON of 1 g/h preceded by a loading dose of 8 g over 30 min. PK sampling was performed for 18 and 24 h in the CON and INT groups, respectively. Fosfomycin was generally well tolerated. However, 2 out of 8 subjects (25%) developed thrombophlebitis at the infusion site following CON, which was prevented in the following subjects with a simultaneous coinfusion of Ringer’s lactate. The steady-state maximum concentration of drug in serum (Cmax) and area under the concentration-time curve from 0 to 24 h at steady state (AUCSS,0–24) of fosfomycin after INT were 551.5 ± 67.8 mg/liter and 3,678.5 ± 601.9 h · mg/liter, respectively. CON led to an average steady-state concentration of 183.8 ± 35.9 mg/liter, resulting in a calculated AUCSS,0–24 of 4,411.2 ± 862.4 h · mg/liter, which was 1.2-fold higher than that with INT. CON resulted in a 100% T>MIC (time during which the drug concentration exceeds the MIC) for MICs of ≤128 mg/liter, whereas the %T>MIC for INT was only 44% for an MIC of 128 mg/liter. CON of fosfomycin led to improved PK and PK/pharmacodynamic (PD) determinants in plasma of healthy volunteers. The clinical relevance of these findings remains to be investigated in patients.

Continuous infusion high-dose cytosine arabinoside in refractory childhood leukemia.

1984 ◽  
Vol 2 (10) ◽  
pp. 1092-1097 ◽  
Author(s):  
J Ochs ◽  
J A Sinkule ◽  
M K Danks ◽  
A T Look ◽  
W P Bowman ◽  
...  
Keyword(s):  
Steady State ◽  
Continuous Infusion ◽  
Cytosine Arabinoside ◽  
Fungal Infections ◽  
Dosage Level ◽  
High Dose ◽  
Loading Dose ◽  
Rapid Infusion ◽  
Organ Systems ◽  
State Plasma

Ten pediatric patients with refractory leukemia received continuous infusion high-dose cytosine arabinoside (ara-C) according to one of two escalating dosage schedules: (1) a 500-mg/m2 rapid infusion loading dose followed by 3.5 g/m2 per day continuous infusion daily for four consecutive days, or (2) a 600-mg/m2 rapid infusion loading dose followed by 5.0 g/m2 per day continuous infusion daily for four consecutive days. Major toxicity at the lower dosage level was grade IV hematopoietic aplasia of three weeks' duration. At the higher dosage level, there was a prohibitive toxicity in multiple organ systems including transient noncardiogenic pulmonary edema, fungal infections, peritonitis, severe diarrhea, transaminase elevations, and one treatment-related death due to acute renal failure. In contrast to other methods of administration of high-dose ara-C, no CNS toxicity occurred. Oncolytic responses were seen in all patients and two achieved brief, partial remissions. Steady-state plasma ara-C concentrations were 13 to 40 mumol/L at the 3.5-g/m2 dosage level and 10 to 225 mumol/L at the 5-g/m2 dosage level; CSF concentrations at both dosages ranged from 2 to 5 mumol/L. Intracellular levels and ratios of 1-beta-D-arabinofuranosylcytidine-5' triphosphate and endogenous deoxycytidine 5' triphosphate in marrow blasts varied widely at steady state during infusion. No positive correlation existed between steady-state plasma ara-C levels, toxicity, oncolytic effect, or intracellular nucleotide concentration.

Effect of Steady-State Enoxacin on Single-Dose Pharmacokinetics of Roflumilast and Roflumilast N-Oxide

2011 ◽  
Vol 51 (4) ◽  
pp. 586-593 ◽  
Author(s):  
Gezim Lahu ◽  
Nassr Nassr ◽  
Rolf Herzog ◽  
Martin Elmlinger ◽  
Peter Ruth ◽  
...  
Keyword(s):  
Single Dose ◽  
Steady State
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