Drawbacks of the constant-infusion technique for measurement of renal function

1995 ◽  
Vol 268 (4) ◽  
pp. F543-F552 ◽  
Author(s):  
B. A. Van Acker ◽  
G. C. Koomen ◽  
L. Arisz
Keyword(s):  
Renal Function ◽  
Steady State ◽  
Plasma Concentrations ◽  
Constant Infusion ◽  
Urinary Recovery ◽  
Infusion Method ◽  
Pah Clearance ◽  
The Difference ◽  
Infusion Technique ◽  
Extrarenal Clearance

We investigated the validity of the steady-state constant infusion method (CIM), in which quantitative urinary recovery and constant plasma concentrations of the solute infused are required. Successive 3-h clearances of inulin and p-aminohippuric acid (PAH) were determined for 27 h in 25 patients with renal disease. Results were compared with the standard method of bladder clearance (StM) and with a modified CIM (ModCIM). The 24-h urinary recovery was incomplete for both inulin and PAH. Mean 24-h ModCIM inulin clearance overestimated StM by 4.5 ml.min-1 x 1.73 m-2 (range 0–9, P < 0.001) independent of the extent of renal impairment and pointed to slow distribution and/or extrarenal clearance of inulin. For PAH, the difference between ModCIM and StM clearance was related to the average PAH clearance by ModCIM and StM (r = 0.78). Furthermore, neither plasma inulin nor PAH became completely constant, because of the circadian rhythm in renal function. In conclusion, the conditions of the steady-state CIM technique are not fulfilled, and the method is not suitable for accurate measurement of inulin and PAH clearance, especially when the clearance is low.

Mivacurium Arteriovenous Gradient during Steady State Infusion in Anesthetized Patients

2002 ◽  
Vol 97 (3) ◽  
pp. 622-629 ◽  
Author(s):  
Samia Ezzine ◽  
François Donati ◽  
France Varin
Keyword(s):  
Steady State ◽  
High Performance ◽  
Sampling Site ◽  
Plasma Concentrations ◽  
Plasma Cholinesterase ◽  
Constant Infusion ◽  
Pharmacokinetic Parameters ◽  
Brachial Vein ◽  
The Difference ◽  
Total Body

Background Mivacurium and isomers undergo rapid hydrolysis by plasma cholinesterase. As this enzyme is largely distributed, it cannot be excluded that these isomers might undergo peripheral elimination. This hypothesis was investigated in patients by measuring the difference between arterial and venous concentrations under a constant-rate continuous infusion of mivacurium. Methods During propofol-remifentanil anesthesia, eight adult consenting patients received an intravenous bolus dose of 0.2 mg/kg mivacurium, followed by a constant infusion (3, 5, or 7 microg. kg. min ) into the brachial vein. One hour after starting the infusion, arterial (radial artery) and venous (contralateral brachial vein) blood samples were drawn simultaneously at 15-min intervals for 45 min. Mivacurium isomers and metabolite plasma concentrations were determined by stereospecific high-performance liquid chromatography. Using the corresponding arterial and venous concentrations, the tissue extraction coefficient as well as total body clearance were calculated. Results During steady state conditions, the venous concentrations of the and isomers were 34 +/- 13% and 42 +/- 11% (mean +/- SD) lower than the corresponding arterial concentrations (P &lt; 0.05), respectively. For the isomer, the difference between venous and arterial concentrations was 3 +/- 4% (P = 0.063). Total body clearances of the and isomers were greater when based on venous sampling (P &lt; 0.05). Conclusion Pharmacokinetic parameters derived from a constant infusion of mivacurium depend heavily on the sampling site (arterial or venous) for the rapidly hydrolyzed isomers. These results strongly suggest a significant metabolism of mivacurium within muscle tissue that may account for the large interpatient variability in response to mivacurium.

Effects of Water-Deprivation on Renal-Function and Plasma Arginine Vasotocin in the Feral Chicken, Gallus-Gallus (Phasianidae)

1991 ◽  
Vol 39 (4) ◽  
pp. 439 ◽  
Author(s):  
JR Roberts
Keyword(s):  
Renal Function ◽  
Water Availability ◽  
Filtration Rate ◽  
Water Deprivation ◽  
Arginine Vasotocin ◽  
Constant Infusion ◽  
Osmotic Minipumps ◽  
Diuretic Hormone ◽  
Infusion Method ◽  
Plasma Arginine

Feral chickens occur on a coral atoll off the coast of Queensland, Australia, where the availability of water is limited. Glomerular filtration rate (GFR) was measured in conscious unrestrained feral chickens by means of osmotic minipumps in fully hydrated birds and in birds subjected to a four-day period of water deprivation. Plasma ionic and osmotic concentrations were measured on each day of the experiment. During water deprivation, body weight decreased and plasma ionic and osmotic concentrations increased. Haematocrit was not significantly affected by dehydration. GFR fell on days 2, 3 and 4 of water deprivation to 62% of hydrated values. The plasma levels of the avian diuretic hormone, arginine vasotocin (AVT), increased by a factor of 2.8 over the period of water deprivation. The sensitivity of release of AVT in the feral chicken is higher than that reported for domestic strains of chickens. This may be related to the ability of the feral strain to survive in regions of limited water availability. GFR was measured also by the 'constant infusion' method, which was not significantly different from GFR measured by osmotic minipumps.

Assessment of methods for improving tracer estimation of non-steady-state rate of appearance

1999 ◽  
Vol 87 (5) ◽  
pp. 1813-1822 ◽  
Author(s):  
A. Gastaldelli ◽  
A. R. Coggan ◽  
R. R. Wolfe
Keyword(s):  
Steady State ◽  
Infusion Rate ◽  
Traditional Approach ◽  
Volume Of Distribution ◽  
Constant Volume ◽  
Constant Infusion ◽  
Steady State Condition ◽  
Fixed Volume ◽  
The One ◽  
Infusion Technique

The most common approach for estimating substrate rate of appearance (Ra) is use of the single-pool model first proposed by R. W. Steele, J. S. Wall, R. C. DeBodo, and N. Altszuler. ( Am. J. Physiol. 187: 15–24, 1956). To overcome the model error during highly non-steady-state conditions due to the assumption of a constant volume of distribution (V), two strategies have been proposed: 1) use of a variable tracer infusion rate to minimize tracer-to-tracee ratio (TTR) variations (fixed-volume approach) or 2) use of two tracers of the same substrate with one infused at a constant rate and the other at a variable rate (variable-volume approach or approach of T. Issekutz, R. Issekutz, and D. Elahi. Can. J. Physiol. Pharmacol. 52: 215–224, 1974). The goal of this study was to compare the results of these two strategies for the analysis of the kinetics of glycerol and glucose under the non-steady-state condition created by a constant infusion of epinephrine (50 ng ⋅ kg−1 ⋅ min−1) with the traditional approach of Steele et al., which uses a constant infusion and fixed volume. The results showed that for glucose and glycerol the estimates of Raobtained with the constant and the variable tracer infusion rate and the equation of Steele et al. were comparable. The variable tracer infusion approach was less sensitive to the choice of V in estimating Ra for glycerol and glucose, although the advantage of changing the tracer infusion rate was greater for glucose than for glycerol. The model of Issekutz et al. showed instability when the ratio TTR1/TTR2approaches a constant value, and the model is more sensitive to measurement error than the constant-volume model for glucose and glycerol. We conclude that the one-tracer constant-infusion technique is sufficient in most cases for glycerol, whereas the one-tracer variable-infusion technique is preferable for glucose. Reasonable values for glucose Ra can be obtained with the constant-infusion technique if V = 145 ml/kg.

scholarly journals Lack of effect of concomitant zidovudine on rifabutin kinetics in patients with AIDS-related complex.

1996 ◽  
Vol 40 (6) ◽  
pp. 1397-1402 ◽  
Author(s):  
R C Li ◽  
S Nightingale ◽  
R C Lewis ◽  
D C Colborn ◽  
P K Narang
Keyword(s):  
Human Immunodeficiency Virus ◽  
Steady State ◽  
Plasma Concentrations ◽  
Urinary Recovery ◽  
Immunodeficiency Virus ◽  
Aids Related Complex ◽  
Safety Parameters ◽  
The Mean ◽  
Interval Ratio ◽  
Related Complex

The effect of concomitant dosing with the antiretroviral agent zidovudine (ZDV) on the pharmacokinetics of rifabutin (RBT) was investigated under steady-state conditions. Sixteen human immunodeficiency virus-positive patients with AIDS-related complex who had been maintained on stable ZDV therapy for > or = 6 weeks were administered RBT concomitantly for 12 days. Eight patients received daily doses of 300 or 450 mg of RBT. Administration of ZDV was discontinued on day 13, and RBT was given alone for 3 additional days. Four patients receiving 450 mg of RBT discontinued treatment. Under steady-state ZDV and RBT dosing, safety and kinetics assessments were performed on day 13 (ZDV plus RBT) and day 16 (RBT alone). Kinetics on days 13 and 16 demonstrated that RBT (300 or 450 mg) was readily absorbed, with the time at which the plasma concentration was maximal (Tmax) ranging between 2.6 and 2.9 h. At these two doses, the mean steady-state maximal plasma concentrations (Cmax) were 250 and 430 ng/ml on day 13 and 245 and 458 ng/ml on day 16, respectively. RBT kinetics at the two doses were proportional and similar on the basis of estimates of the ratios of the areas under the concentration-time curves over the dosing interval from 0 to 24 h (AUC0-24) (450 mg/300 mg), which were 1.5 and 1.4 for days 13 and 16, respectively. No significant differences were apparent in the mean oral clearance (CLs/F) estimates (range, 1.60 to 1.77 liters/h/kg), which were dose independent and similar for the 2 assessment days, as was the urinary recovery of RBT and its 25-deacetyl metabolite. Low urinary recovery of 25-deacetyl RBT and an AUC metabolite/parent ratio of 0.1 suggest that there is minimal metabolism of RBT via the deacetylation pathway. For RBT, pooled mean (95% confidence interval) ratio (day 13/day 16) estimates for Cmax, Tmax, AUC0-24, and CLs/F were 1.07 (range, 0.77 to 1.38), 1.08 (0.89 to 1.27), 0.97 (0.82 to 1.13), and 1.09 (0.92 to 1.26), respectively. In addition, no significant changes in any of the major safety parameters were detected throughout the study. Therefore, it is concluded that coadministration of ZDV and RBT does not affect the pharmacokinetics and/or safety of RBT in human immunodeficiency virus-positive patients.

Secretory dynamics of 1α-hydroxycorticosterone in the elasmobranch fish, Scyliorhinus canicula

1984 ◽  
Vol 103 (2) ◽  
pp. 205-211 ◽  
Author(s):  
N. Hazon ◽  
I. W. Henderson
Keyword(s):  
Sodium Chloride ◽  
Sea Water ◽  
Specific Activity ◽  
Plasma Concentrations ◽  
High Specific Activity ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Plasma Osmolarity ◽  
Scyliorhinus Canicula ◽  
Infusion Technique

ABSTRACT Peripheral plasma concentrations, metabolic clearance rates (MCR) and blood production rates (BPR) of 1α-hydroxycorticosterone (1-OH-B) were determined in female dogfish (Scyliorhinus canicula) under varying environmental conditions. The constant-infusion technique, using high specific activity tritiated 1-OH-B, was applied to measure the MCR, and BPR were derived from the product of plasma concentration and MCR at equilibrium. Urea plasma clearances and apparent BPR were assessed in a similar manner. Fish were adapted stepwise to 140, 120, 90, 80, 70, 60 and 50% normal sea water (about 1000 mosmol/l). In all cases 1-OH-B was the major corticosteroid, cortisol and corticosterone were sought but never detected. In environments of reduced osmolarity, plasma osmolarity, sodium, chloride and urea concentrations all declined, alongside increases in plasma concentrations, MCR and BPR of 1-OH-B. In fish held in environments at concentrations greater than normal sea water, plasma osmolarity, sodium, chloride and urea concentrations all increased. Plasma clearance of urea increased in fish held in environments more dilute than sea water, while it decreased in the more hyperosmotic waters. It is tentatively concluded that homeostasis of plasma composition, with particular respect to urea, is in part regulated by 1-OH-B in the dogfish. J. Endocr. (1984) 103, 205–211

MR Velocity Mapping Measurement of Renal Artery Blood Flow in Patients with Impaired Kidney Function

1996 ◽  
Vol 37 (1P1) ◽  
pp. 79-84 ◽  
Author(s):  
M. Cortsen ◽  
L. J. Petersen ◽  
F. Ståhlberg ◽  
C. Thomsen ◽  
L. Søndergaard ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Function ◽  
Kidney Function ◽  
Pulse Sequence ◽  
Renal Plasma Flow ◽  
Image Plane ◽  
Renal Arteries ◽  
Constant Infusion ◽  
Velocity Mapping ◽  
Pah Clearance

Renal blood flow (RBF) was measured in 9 patients with chronic impaired kidney function using MR velocity mapping and compared to PAH clearance and 99mTc-DTPA scintigraphy. An image plane suitable for flow measurement perpendicular to the renal arteries was chosen from 2-dimensional MR angiography. MR velocity mapping was performed in both renal arteries using an ECG-triggered gradient echo pulse sequence previously validated in normal volunteers. Effective renal plasma flow was calculated from the clearance rate of PAH during constant infusion and the split of renal function was evaluated by 99mTc-DTPA scintigraphy. A reduction of RBF was found, and there was a significant correlation between PAH clearance multiplied by 1/(1-hematocrit) and RBF determined by MR velocity mapping. Furthermore a significant correlation between the distribution of renal function and the percent distribution of RBF was found.

Measurement of urea kinetics in vivo by means of a constant tracer infusion of di-15N-urea

1981 ◽  
Vol 240 (4) ◽  
pp. E428-E434 ◽  
Author(s):  
R. R. Wolfe
Keyword(s):  
Steady State ◽  
Constant Infusion ◽  
Selected Ion Monitoring ◽  
Plasma Urea ◽  
Urea Production ◽  
Nonsteady State ◽  
Urea Metabolism ◽  
The Difference ◽  
15N Urea

We have assessed the feasibility of studying urea metabolism in vivo in both steady state and nonsteady state situations by means of the primed constant infusion of di-15N-urea and the analysis of the resulting enrichment in plasma urea. Both hepatectomized dogs with known rates of urea infusion and intact dogs were studied. The enrichment of the bistrimethylsilyl derivative of urea was determined on a gas chromatograph-mass spectrometer. Selected ion monitoring was set for m/e 189 (M - 15), m/e 190 (A + 1), and m/e 191 (A + 2), thus enabling the calculation of the rate of urea production from nonrecycled NH3 (from A + 2 data) (Ra N), the rate of recycling of NH3 into urea (Ra R) (from A + 1 data), and thus the total rate of urea production (Ra N + Ra R). When urine collections were made, the incorporation of urea-N into protein was estimated from the difference between Ra N and urea excretion. We found that, in the steady state in a hepatectomized dog, the rate of appearance of urea can be determined accurately. In the nonsteady state in both hepatectomized and intact dogs, urea appearance could be estimated within +/- 20% in most situations. The only situation in which this was not the case was when we attempted to measure rapid changes in Ra R. Thus, within limits, this can be a useful technique enabling the quantitation of various aspects of urea metabolism.

Dosing of troxacitabine (Troxatyl [T], SGX-145) based on renal function

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2025-2025
Author(s):  
M. J. Kelner ◽  
F. J. Giles ◽  
E. J. Feldman ◽  
G. J. Roboz ◽  
D. J. Deangelo ◽  
...  
Keyword(s):  
Renal Function ◽  
Steady State ◽  
Creatinine Clearance ◽  
Plasma Concentrations ◽  
Myelogenous Leukemia ◽  
Blood Levels ◽  
Upper Limit ◽  
Major Route ◽  
Cancer Agent ◽  
Dosing Strategy

2025 Background: Troxacitabine (Troxatyl [T], SGX-145) is a novel L-configuration nucleoside analog anti-cancer agent with unique mechanistic/cytotoxic properties. T is clinically active against acute myelogenous leukemia (AML), chronic myeloid leukemia, myelodysplastic syndromes (MDS), renal cell carcinoma, and pancreatic cancer. A multi-center Phase 2/3 clinical trial is currently underway to evaluate the safety and efficacy of continuous IV infusion T treatment in second salvage AML. The major route of elimination of troxacitabine is renal excretion as unchanged drug (∼70%) and there is minimal protein binding. These results suggest that renal function may have a significant effect on steady-state troxacitabine plasma concentrations (Css). Methods: Pharmacokinetic and toxicity data from four AML clinical trials (>200 patients) are being analyzed to (1) Identify a minimum Css for therapeutic efficacy; (2) Define an upper limit of Css for adverse risk; and (3) Develop a mechanism to prospectively modify the troxacitabine dose based on renal function, which would avoid excessive toxicity while maintaining therapeutic blood levels. Results: Initial results from 41 patients indicate that to induce remission in AML patients, troxacitabine steady-state plasma concentrations (Css) must be ≥ 80 ng/mL. However, higher Css values correlate with increased toxicity and, thereby, increase the risks of the treatment for an individual patient, although an upper limit for adverse risk has not yet been defined. For patients with normal renal function (creatinine clearance ≥ 50 but ≤ 125 mL/min), a Calvert style formula, based on a patient’s estimated creatinine clearance, has been developed to define the dose required to achieve a therapeutic Css ≥ 80 ng/mL. Both linear and non-linear nomogram models are also being developed to adjust troxacitabine dosage for patients with moderate renal impairment (30 mL/min < creatinine clearance < 50 mL/min) or for patients with high GFR (creatinine clearance > 125 mL/min). Conclusion: A firm relationship exists between renal function, troxacitabine clearance, and Css values. This result indicates that a dosing strategy based on renal function may be warranted to obtain optimal troxacitabine Css values. [Table: see text]

Serial Overnight Recordings of Intracarpal Canal Pressure in Carpal Tunnel Syndrome Patients with and without Wrist Splinting

1994 ◽  
Vol 19 (1) ◽  
pp. 35-37 ◽  
Author(s):  
R. LUCHETTI ◽  
R. SCHOENHUBER ◽  
M. ALFARANO ◽  
S. DELUCA ◽  
G. DE CICCO ◽  
...  
Keyword(s):  
Carpal Tunnel Syndrome ◽  
Carpal Tunnel ◽  
Critical Pressure ◽  
Constant Infusion ◽  
Tunnel Syndrome ◽  
The Difference ◽  
Infusion Technique

In 15 carpal tunnel syndrome patients pressure was measured during the day and at 2-hourly intervals from midnight to 6 a.m., via a catheter introduced into the carpal canal, using the constant infusion technique. Intracarpal tunnel pressure of the patients always exceeded the critical pressure of 30 mmHg and the highest values were found at 6 a.m. Slightly lower pressures were found when the wrist was splinted, but the difference was not significant, nor were critical pressure levels prevented by splinting.

Effect of nitrendipine on renal function and on hormonal parameters after intravascular iopromide

1998 ◽  
Vol 39 (4) ◽  
pp. 375-380 ◽  
Author(s):  
J. K. Madsen ◽  
L. Winther Jensen ◽  
J. Sandermann ◽  
N. Johannesen ◽  
W. P. Paaske ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Renal Plasma Flow ◽  
Randomized Study ◽  
Atherosclerotic Disease ◽  
Constant Infusion ◽  
Double Blind ◽  
Blood Pressure Treatment ◽  
Renal Tubular ◽  
Infusion Technique

Purpose: To evaluate the effect of the low-molecular nonionic radiographic contrast agent iopromide (Ultravist) on renal function, vasoactive peptides (angiotensin II, aldosterone, arginine vasopressin, and atrial natriuretic factor (ANF)), and blood pressure, and to evaluate the influence of the calcium antagonist nitrendipine on these parameters. The findings were evaluated in a prospective, double-blind and placebo-controlled randomized study. Material and Methods: Twenty-six patients undergoing routine aortofemoral arteriography for peripheral atherosclerotic disease were treated with nitrendipine tablets (10 mg) or placebo twice daily for a week. Angiography was performed on the fifth day of medication. Efficacy variables were determined on the day before and 2 days after arteriography. The glomerular filtration rate and renal plasma flow were measured by the constant infusion technique. Renal tubular function was estimated from the clearance of lithium. Hormones were measured by radioimmunoassays. Results: Arteriography with iopromide did not change renal function. No differences between the nitrendipine and placebo groups were found in renal hemodynamics, tubular sodium handling, or blood pressure. Nitrendipine changed ANF (26.1%) compared to placebo (1.5%), whereas the other hormones were not affected. Conclusion: The use of iopromide for angiography did not affect renal function in normotensive patients with peripheral atherosclerotic disease. Shortterm treatment with nitrendipine may lower the plasma levels of ANF but it had no effect on renal function or blood pressure. Treatment with calcium antagonists prior to arteriography with iopromide is not indicated in these patients.

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