Reassessment of the single intravenous injection method with inulin for measurement of the glomerular filtration rate in man

1991 ◽  
Vol 80 (2) ◽  
pp. 167-176 ◽  
Author(s):  
L. F. Prescott ◽  
S. Freestone ◽  
J. A. N. McAuslane
Keyword(s):  
Renal Failure ◽  
Healthy Volunteers ◽  
Renal Clearance ◽  
Single Injection ◽  
Linear Regression Analysis ◽  
Constant Infusion ◽  
Injection Method ◽  
Renal Clearances ◽  
Infusion Method ◽  
Total Body

1. Factors influencing the total body and renal clearances of inulin were investigated in a total of 37 healthy adult volunteers and 10 patients with stable chronic renal failure after the single intravenous injection of a dose of 70 mg/kg given over 5 min. 2. The elimination of inulin was highly concentration-dependent, and in healthy volunteers the renal clearance fell from 103.7 ± 14.4 ml min−1 1.73 m−2 during the first hour after administration to 49.1 ± 20.9 ml min−1 1.73 m−2 over the period 6-8 h. In the patients with renal failure the renal clearance fell correspondingly from 39.7 ± 16.5 to 26.6 ± 8.6 ml min−1 1.73 m−2. There were no changes in the simultaneously measured clearances of creatinine. 3. The values obtained for the total body clearance of inulin after a single injection depend critically on dose, the number and timing of blood samples, the choice of pharmacokinetic model, the number of data points chosen for estimation of the slope of the terminal elimination phase for analysis by the methods of residuals, and the weighting used for curve fitting by non-linear regression analysis. 4. With standardized conditions of sampling from 0 to 2 h and weighted non-linear regression analysis of the plasma concentration-time data, the total body and renal clearances of inulin were almost identical in subjects with normal renal function at 105.2 ± 10.2 and 102.9 ± 13.0 ml min−1 1.73 m−2. In the patients with chronic renal failure sampling was continued for 3 h and the corresponding clearances were 40.4 ± 15.3 and 38.9 ± 15.7 ml min−1 1.73 m−2. 5. The 0-2 h total body and renal clearances of inulin were measured by the single injection method and the renal clearance was measured by the standard constant infusion method on different occasions in 10 healthy volunteers. The respective clearances were similar at 101.4 ± 6.6, 94.9 ± 11.9 and 88.4 ± 12.1 ml min−1 1.73 m−2. 6. The reproducibility of the single injection and constant infusion methods was compared by measuring the inulin clearance with both techniques on three occasions in separate groups of eight and nine healthy volunteers. The mean coefficient of variation for the total body clearance with the single injection method was only 3.9% compared with 9.5% for the renal clearance determined the same way and 12.0% for the renal clearance during constant infusion. 7. Urine collection and fluid loading are not required for the single injection technique, and it is more reproducible and less demanding than the constant infusion method. With simple precautions, the single injection method with inulin is suitable for routine estimation of the glomerular filtration rate.

Renal Clearance of [14C]oxalate: Comparison of Constant-Infusion with Single-Injection Techniques

1982 ◽  
Vol 63 (1) ◽  
pp. 47-51 ◽  
Author(s):  
J. A. C. Prenen ◽  
P. Boer ◽  
E. J. Dorhout Mees ◽  
H. J. Endeman ◽  
S. M. Spoor ◽  
...  
Keyword(s):  
Healthy Volunteers ◽  
Renal Clearance ◽  
Single Injection ◽  
Compartment Model ◽  
Constant Infusion ◽  
Injection Technique ◽  
Clearance Ratio ◽  
Urine Sampling ◽  
Two Compartment Model ◽  
Infusion Technique

1. The renal clearance of [14C]oxalate was assessed by the constant-infusion technique and single-injection technique (plasma sampling only: one-compartment and two-compartment model; plasma and urine sampling). Healthy volunteers and patients with renal stones were studied. 2. Results with the constant-infusion techniques (with and without urine sampling) were not significantly different from each other. 3. The renal clearance of [14C]oxalate measured with the single-injection technique as compared with the constant-infusion technique was overestimated in the single-injection one-compartment model (52%) as well as in the two-compartment model (30%). 4. The calculated level of plasma oxalate in the healthy volunteers ranged from 1·04 to 1·78 μmol/l (mean 1·39). 5. The biological half-life of [14C]oxalate, estimated by the cumulative excretion of 14C in urine after equilibrium had been established, was 128 min (range: 113–142). 6. The oxalate/creatinine clearance ratio in the healthy volunteers ranged from 1·73 to 2·22 (mean 2·01).

Estimation of hepatic blood flow using a single injection dye clearance method

1960 ◽  
Vol 198 (4) ◽  
pp. 877-880 ◽  
Author(s):  
Edward F. Banaszak ◽  
William J. Stekiel ◽  
Robert A. Grace ◽  
James J. Smith
Keyword(s):  
Blood Flow ◽  
Hepatic Blood Flow ◽  
Plasma Flow ◽  
Single Injection ◽  
Venous Blood ◽  
Constant Infusion ◽  
Injection Method ◽  
Practical Standpoint ◽  
The Mean ◽  
Peripheral Arterial

In dogs anesthetized with morphinesodium barbital, hepatic blood flow was estimated from the concentration-time slopes of peripheral arterial and hepatic venous blood following a single injection of either indocyanine or BSP. The injection of indocyanine in doses ranging from 5 to 50 mg produced 20-minute decay slopes which were logarithmic. The mean estimated hepatic plasma flow in 25 dogs using indocyanine was 23 ± 1.3 ml/kg/min. and the mean estimated hepatic blood flow was 43 ± 2.2 ml/kg/min. These mean blood flow values were about 12% higher than the hepatic blood flows estimated with Bradley's constant infusion (BSP) method but there was quite close agreement in hepatic plasma flow values with the two methods. The mean indocyanine space in 25 dogs was 49 ± 1.4 ml/kg. Indocyanine appears to be preferable to BSP for use with the single injection method. From a theoretical as well as practical standpoint, the single injection method appears to have potential usefulness for the estimation of hepatic blood flow.

Pharmacokinetics of Intravenous and Oral Pindolol in Hypertensive Patients with Chronic Renal Failure

1978 ◽  
Vol 55 (s4) ◽  
pp. 275s-277s
Author(s):  
M. E. Safar ◽  
N. Ph. Chau ◽  
J. A. Levenson ◽  
A. Ch. Simon ◽  
Y. A. Weiss
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Chronic Renal Failure ◽  
Renal Clearance ◽  
Normal Renal Function ◽  
Initial Rate ◽  
Hepatic Clearance ◽  
Hypertensive Patients ◽  
Rate Of Absorption ◽  
Total Body

1. The pharmacokinetics of intravenous and oral pindolol were determined in 24 hypertensive patients with normal or impaired renal function. 2. In patients with normal renal function, the total clearance of the drug was the sum of both the renal and non-renal clearances in equal parts. The non-renal clearance was found to equal the hepatic clearance directly measured from the hepatic extraction ratio and hepatic blood flow. 3. Compared with patients with normal renal function, patients with chronic renal failure exhibited (i) unchanged transfer rate constants and distribution volumes, (ii) decreased total body clearance with decreased renal clearance and unchanged non-renal clearance. 4. Analysis of data obtained after oral administration of the drug by the Loo—Riegelman method showed that the pindolol absorption kinetic was non-linear. Compared with patients with normal renal function, patients with chronic renal failure exhibited (i) a significantly decreased fraction of dose effectively absorbed, (ii) an increased initial rate of absorption. The initial rate of absorption was inversely correlated with creatinine clearance. 5. The study provided evidence that in patients with renal insufficiency, (i) no increase in the metabolism of the drug accompanied the decrease in renal function, and (ii) decreased bio-availability was associated with a reduced fraction of the dose effectively absorbed and an increased rate of absorption.

scholarly journals Osmotically inactive sodium and potassium storage: lessons learned from the Edelman and Boling data

2016 ◽  
Vol 311 (3) ◽  
pp. F539-F547 ◽  
Author(s):  
Minhtri K. Nguyen ◽  
Dai-Scott Nguyen ◽  
Minh-Kevin Nguyen
Keyword(s):  
Linear Regression ◽  
Measurement Errors ◽  
Linear Regression Analysis ◽  
Sodium Concentration ◽  
Lessons Learned ◽  
Dynamic Changes ◽  
Data Set ◽  
Storage Pool ◽  
Total Body ◽  
Sodium And Potassium

Because changes in the plasma water sodium concentration ([Na+]pw) are clinically due to changes in the mass balance of Na+, K+, and H2O, the analysis and treatment of the dysnatremias are dependent on the validity of the Edelman equation in defining the quantitative interrelationship between the [Na+]pw and the total exchangeable sodium (Nae), total exchangeable potassium (Ke), and total body water (TBW) (Edelman IS, Leibman J, O'Meara MP, Birkenfeld LW. J Clin Invest 37: 1236–1256, 1958): [Na+]pw = 1.11(Nae + Ke)/TBW − 25.6. The interrelationship between [Na+]pw and Nae, Ke, and TBW in the Edelman equation is empirically determined by accounting for measurement errors in all of these variables. In contrast, linear regression analysis of the same data set using [Na+]pw as the dependent variable yields the following equation: [Na+]pw = 0.93(Nae + Ke)/TBW + 1.37. Moreover, based on the study by Boling et al. (Boling EA, Lipkind JB. 18: 943–949, 1963), the [Na+]pw is related to the Nae, Ke, and TBW by the following linear regression equation: [Na+]pw = 0.487(Nae + Ke)/TBW + 71.54. The disparities between the slope and y-intercept of these three equations are unknown. In this mathematical analysis, we demonstrate that the disparities between the slope and y-intercept in these three equations can be explained by how the osmotically inactive Na+ and K+ storage pool is quantitatively accounted for. Our analysis also indicates that the osmotically inactive Na+ and K+ storage pool is dynamically regulated and that changes in the [Na+]pw can be predicted based on changes in the Nae, Ke, and TBW despite dynamic changes in the osmotically inactive Na+ and K+ storage pool.

Studies on the mechanism of the selective suppression of plasma levels of follicle-stimulating hormone in the female rat after administration of steroid-free bovine follicular fluid

1983 ◽  
Vol 97 (3) ◽  
pp. 327-338 ◽  
Author(s):  
W. J. de Greef ◽  
F. H. de Jong ◽  
J. de Koning ◽  
J. Steenbergen ◽  
P. D. M. van der Vaart
Keyword(s):  
Follicular Fluid ◽  
Plasma Levels ◽  
Single Injection ◽  
Constant Infusion ◽  
Metabolic Clearance ◽  
Female Rat ◽  
Clearance Rates ◽  
Lh Rh ◽  
Lh Releasing Hormone ◽  
Hypophysial Portal

Steroid-free bovine follicular fluid (bFF) selectively suppresses the plasma levels of FSH in the female rat, demonstrating that bFF contains inhibin-like material. The present study was concerned with the effects of bFF on the hypothalamic release of LH releasing hormone (LH-RH) into hypophysial stalk blood and on the metabolic clearance rates of gonadotrophins. The metabolic clearance rates of FSH, LH and prolactin were determined after a single injection of and during a constant infusion with adenohypophysial extract. Similar results were obtained with both methods, and treatment with bFF did not alter the metabolic clearance rates of FSH, LH and prolactin. Anaesthesia with urethane, used for surgery involved in the collection of hypophysial stalk blood, did not interfere with the effect of bFF on plasma levels of FSH. The administration of bFF did not change the hypothalamic content of LH-RH, but caused a 30% decrease in the levels of LH-RH in hypophysial stalk plasma. However, a fraction isolated from bFF, which contained 20 times more inhibin-like activity per mg protein than bFF, did not alter the hypothalamic release of LH-RH into the hypophysial portal blood while this fraction was effective in specifically suppressing the plasma levels of FSH. It was concluded that the inhibin-like activity in bFF does not suppress the plasma levels of FSH by affecting its plasma clearance or by influencing the hypothalamic release of LH-RH, but that it has a direct effect on the adenohypophysis in inhibiting the release of FSH. Besides the inhibin-like activity, bFF also contains another factor which can decrease the levels of LH-RH in hypophysial stalk plasma.

Disturbed lipoprotein composition in non-dialyzed, hemodialysis, continuous ambulatory peritoneal dialysis and post-transplant patients with chronic renal failure

2006 ◽  
Vol 44 (1) ◽  
Author(s):  
Elżbieta Kimak ◽  
Andrzej Książek ◽  
Janusz Solski
Keyword(s):  
Renal Failure ◽  
Peritoneal Dialysis ◽  
Chronic Renal Failure ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Healthy Subjects ◽  
Linear Regression Analysis ◽  
Multivariate Linear Regression Analysis ◽  
Post Transplant ◽  
Transplant Patients ◽  
Lipoprotein Composition

AbstractStudies were carried out in 183 non-dialyzed, 123 hemodialysis, 81 continuous ambulatory peritoneal dialysis and 35 post-transplant patients and in 103 healthy subjects as a reference group. Lipids and apolipoprotein (apo)AI and apoB were determined using Roche kits. An anti-apoB antibody was used to separate apoB-containing apoCIII and apoE-triglyceride-rich lipoprotein (TRL) in the non-high-density lipoprotein (non-HDL) fraction from apoCIIInonB and apoEnonB in the HDL fraction in four groups of patients with chronic renal failure (CRF) and healthy subjects. Multivariate linear regression analysis was used to investigate the relationship between triglyceride (TG) or HDL-cholesterol (HDL-C) concentrations and lipoproteins. Dyslipidemia varied according to the degree of renal insufficiency, the type of dialysis and therapy regime in CRF patients. Lipoprotein disturbances were manifested by increased TG, non-HDL-C and TRL concentrations, and decreased HDL-C and apoAI concentrations, whereas post-renal transplant patients showed normalization of lipid and lipoprotein profiles, except for TG levels and total apoCIII and apoCIIInonB. The present study indicates that CRF patients have disturbed lipoprotein composition, and that hypertriglyceridemia and low HDL-C concentrations in these patients are multifactorial, being secondary to disturbed lipoproteins. The method using anti-apoB antibodies to separate apoB-containing lipoproteins in the non-HDL fraction from non-apoB-containing lipoproteins in HDL can be used in the diagnosis and treatment of patients with progression of renal failure or atherosclerosis. The variability of TG and HDL-C concentrations depends on the variability of TRL and cholesterol-rich lipoprotein concentrations, but the decreases in TG and increases in HDL-C concentrations are caused by apoAI concentration variability. These relationships, however, need to be confirmed in further studies.

scholarly journals Comparable Population Pharmacokinetics and Pharmacodynamic Breakpoints of Cefpirome in Cystic Fibrosis Patients and Healthy Volunteers

2011 ◽  
Vol 55 (6) ◽  
pp. 2927-2936 ◽  
Author(s):  
J. B. Bulitta ◽  
M. Kinzig ◽  
C. B. Landersdorfer ◽  
U. Holzgrabe ◽  
U. Stephan ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Healthy Volunteers ◽  
High Performance ◽  
Standard Dose ◽  
Total Body Weight ◽  
Volume Of Distribution ◽  
Nonparametric Bootstrap ◽  
Population Pk ◽  
Total Body ◽  
Similar Body

ABSTRACTCystic fibrosis (CF) patients are often reported to have higher clearances and larger volumes of distribution per kilogram of total body weight (WT) for beta-lactams than healthy volunteers. As pharmacokinetic (PK) data on cefpirome from studies of CF patients are lacking, we systematically compared its population PK and pharmacodynamic breakpoints for CF patients and healthy volunteers of similar body size. Twelve adult CF patients (median lean body mass [LBM] = 45.7 kg) and 12 healthy volunteers (LBM = 50.0 kg) received a single 10-min intravenous infusion of 2 g cefpirome. Plasma and urine concentrations were determined by high-performance liquid chromatography (HPLC). Population PK and Monte Carlo simulations were performed using NONMEM and S-ADAPT and a duration of an unbound plasma concentration above the MIC ≥ 65% of the dosing interval as a pharmacodynamic target. Unscaled clearances for CF patients were similar to those seen with healthy volunteers, and the volume of distribution was 6% lower for CF patients. Linear scaling of total clearance by WT resulted in clearance that was 20% higher (P≤ 0.001 [nonparametric bootstrap]) in CF patients. Allometric scaling by LBM explained the differences between the two subject groups with respect to average clearance and volume of distribution and reduced the unexplained between-subject variability of renal and nonrenal clearance by 10 to 14%. For the CF patients, robust (>90%) probabilities of target attainment (PTA) were achieved by the administration of a standard dose of 2 g/70 kg WT every 12 h (Q12h) given as 30-min infusions for MICs ≤ 1.5 mg/liter. As alternative dosage regimens, a 5-h infusion of 1.33 g/70 kg WT Q8h achieved robust PTAs for MICs ≤ 8 to 12 mg/liter and a continuous infusion of 4 g/day for MICs ≤ 12 mg/liter. Prolonged infusion of cefpirome is expected to be superior to short-term infusions for MICs between 2 and 12 mg/liter.

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