scholarly journals Contribution of Renal and Non-Renal Clearance on Increased Total Clearance of Adalimumab in Glomerular Disease

2013 ◽  
Vol 53 (9) ◽  
pp. 919-924 ◽  
Author(s):  
Brittney V. Roberts ◽  
Isidro Susano ◽  
Debbie S. Gipson ◽  
Howard Trachtman ◽  
Melanie S. Joy
2016 ◽  
pp. S489-S497 ◽  
Author(s):  
J. CERMANOVA ◽  
A. PRASNICKA ◽  
E. DOLEZELOVA ◽  
L. ROZKYDALOVA ◽  
M. HROCH ◽  
...  

The aim of the present study was to describe the currently poorly understood pharmacokinetics (PK) of boldine in control rats (LW, Lewis rats), and Mrp2 transporter-deficient rats (TR-). Animals from the LW and TR- groups underwent a bolus dose study with 10 mg/kg of boldine applied either orally or intravenously in order to evaluate the major PK parameters. The TR- rats demonstrated significantly reduced total clearance with prolonged biological half-life (LW 12±4.6 versus TR- 20±4.4 min), decreased volume of distribution (LW 3.2±0.4 l/kg versus TR- 2.4±0.4 l/kg) and reduced bioavailability (LW 7 % versus TR- 4.5 %). Another set of LW and TR- rats were used for a clearance study with continuous intravenous administration of boldine. The LW rats showed that biliary and renal clearance formed less than 2 % of the total clearance of boldine. The treatment of samples with β glucuronidase showed at least a 38 % contribution of conjugation reactions to the overall clearance of boldine. The TR- rats demonstrated reduced biliary clearance of boldine and its conjugates, which was partly compensated by their increased renal clearance. In conclusion, this study presents the PK parameters of boldine and shows the importance of the Mrp2 transporter and conjugation reactions in the elimination of the compound.


1989 ◽  
Vol 7 (2) ◽  
pp. 270-275 ◽  
Author(s):  
P A Reece ◽  
I Stafford ◽  
R L Abbott ◽  
C Anderson ◽  
J Denham ◽  
...  

The disposition of unchanged cisplatin was compared after two- and 24-hour intravenous (IV) infusion to eight patients with germ cell cancer (dose, 100 mg/m2), 14 patients with head and neck cancer (dose, seven patients 50 mg/m2; seven patients, 100 mg/m2). Patients were randomized to receive either a two- or 24-hour infusion in the first course of treatment and the reverse in the second course. Cisplatin renal clearance, total clearance, and the percentage of the dose excreted unchanged in urine were significantly lower with the longer infusion. Total clearance was 345 +/- 97.0 mL/min/m2 after the two-hour infusion and 268 +/- 70.7 mL/min/m2 after the 24-hour infusion (P less than .0001). Renal clearance was 79.1 +/- 35.3 mL/min/m2 and 34.1 +/- 14.9 mL/min/m2 (P less than .0001). The percentage of the dose excreted unchanged in urine was 22.9 +/- 6.5% and 12.8 +/- 4.0%, respectively (P less than .0001). The ratio of cisplatin renal clearance to creatinine clearance was 1.95 +/- .96 after the two-hour infusion and .90 +/- .40 after the 24-hour infusion (P less than .001). There was only a poor relationship between cisplatin renal clearance and creatinine clearance after a two-hour infusion (r2 = .05, P greater than .1) or 24-hour infusion (r2 = .18, P greater than .05). The severity of emesis was graded on a four-point scale and was significantly less with the 24-hour infusion than with the two-hour infusion (P less than .05). Twenty-four-hour infusion of cisplatin resulted in greater drug retention in patients due to reduced renal clearance, but was also associated with reduced emetic toxicity, probably as a result of lower peak plasma levels.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Joyce Pinto ◽  
Malgorzata Debowska ◽  
Rafael Gomez ◽  
Jacek Waniewski ◽  
Bengt Lindholm

Abstract Background and Aims In dialysis patients, urine volume is an easy-to-obtain marker of residual kidney function but information is lacking of its potential value as an estimate of the renal contribution to total clearance of small solutes. We explored whether correlations of urine volume with different estimations of the residual renal function for urea, creatinine, and phosphorus, could be used to assess renal solute clearances and renal mass removal for investigated solutes. Method In an observational study of 94 non-anuric (urine output ≥ 100 mL per 24 hours) patients (54% men, median age 59 [45 - 68] year, BMI 25.8 [21.4 - 27.7] kg/m2) undergoing automated (n = 59) or continuous ambulatory (n = 35) peritoneal dialysis (PD), we evaluated renal, peritoneal and total (renal plus peritoneal) solute removal (g/week) and clearance (L/week) in relation to urine volume (L/day). Urine volume, renal clearances, ratio of urine solute to serum solute concentration, removed mass of each solute and the ratio of mass removed by urine (renal clearance) over total mass removed by urine and dialysate (total clearance) for urea, creatinine and phosphorus were estimated from 24 h collections of urine and dialysate and determination of solute concentrations in serum, urine and dialysate. Statistical dependence between variables was tested using Spearman’s correlation coefficient (rho). Data are expressed as median with interquartile range. Results Median 24-hour urine output was 560 [323 – 938] mL. Renal mass removal for urea, creatinine and phosphorus was 10.1 [4.5 – 17.1], 3.5 [1.8 – 5.6] and 1.0 [0.4 – 1.7] g/week, respectively. The average contribution of residual renal removal to the total mass removed was 28% [17% - 41%] for urea, 56% [30% - 72%] for creatinine and 44% [24% - 58%] for phosphorus. Serum creatinine correlated weakly and negatively with urine volume (rho = -0.26, p < 0.05), but no such relationship was observed for urea and phosphorus. Only urine concentration of creatinine correlated weakly with urine volume with rho = -0.28 and p < 0.01. Urine concentration over plasma concentration did not correlate with urine volume for any solute. Renal urea clearance (20.1 [11.4 - 35.7] L/week) correlated positively with creatinine renal clearance (43.0 [18.9 - 75.1] L/week), (rho = 0.92), and with phosphorus renal clearance (17.3 [7.6 - 32.9] L/week), (rho = 0.89, p < 0.001; Fig. 1A), while renal creatinine clearance correlated positively with phosphorus renal clearance (rho = 0.86, p<0.001). Urine volume correlated positively with urea, creatinine and phosphorus clearances at rho 0.78, 0.63 and 0.73, respectively (all p< 0.001), and with renal removal of mass of urea, creatinine, and phosphorus with rho= 0.83, 0.68 and 0.74 (Fig. 1B), respectively; all p<0.001. Conclusion In PD patients, solute renal clearances and renal mass removal for urea, creatinine and phosphorus may be predicted from urine volume. Among renal clearances for urea, creatinine, and phosphorus two of them may be assessed based on measurements of the third one.


2015 ◽  
Vol 40 (4) ◽  
pp. 521-522 ◽  
Author(s):  
Charles Frost ◽  
Rebecca A. Boyd

2006 ◽  
Vol 50 (12) ◽  
pp. 4186-4188 ◽  
Author(s):  
Takahiro Shibayama ◽  
Yoko Matsushita ◽  
Takashi Hirota ◽  
Toshihiko Ikeda ◽  
Shogo Kuwahara

ABSTRACT The CS-023 concentration in plasma after administration by infusion to healthy volunteers at a dose of 700 mg was decreased, with a half-life of 1.7 h, and the cumulative urinary excretion was 59.4% of the dose. The total clearance, renal clearance, and volume of distribution were 8.12 liters/h, 4.14 liters/h, and 17.2 liters, respectively.


1991 ◽  
Vol 261 (3) ◽  
pp. R665-R669 ◽  
Author(s):  
R. Keeler ◽  
A. K. Sato ◽  
J. R. Claybaugh ◽  
N. Wilson

Isolated rat kidneys were perfused with Krebs-Henseleit-bovine serum albumin solution at a mean pressure of 99 +/- 2.6 mmHg. After control periods, arginine vasopressin (AVP) was added to the perfusate at a final calculated concentration of 25 pg/ml (2.5 x 10(-11) M). Urine and perfusate samples were collected at 15-min intervals for the following 60 min to measure kidney function and the renal clearance of immunoreactive AVP (irAVP). At 15-30 min after the addition of AVP, total renal clearance of irAVP was 1,623 +/- 190 microliters.min-1.g kidney wt-1. Glomerular filtration accounted for 35 +/- 3.0% of the total clearance, and 65 +/- 10.3% was cleared by peritubular pathways. Of the filtered irAVP, 48 +/- 4.8% was recovered in the urine. To investigate the importance of V2 receptors in the metabolism of AVP, clearance measurements were made in the presence of the V2 antagonist [d(CH2)5,D-Ile2,Ile4,Arg8]AVP (5 x 10(-9) M). Total renal clearance of irAVP was reduced by 48% to 848 +/- 79 microliters.min-1.g-1. This reduction was entirely accounted for by the complete inhibition of peritubular clearance of irAVP. In the presence of the V2 antagonist, irAVP was cleared only by filtration. The proportion of filtered AVP recovered in the urine (53 +/- 8.7%) was not significantly altered by the presence of the V2 antagonist. We conclude that a major component of the renal clearance of AVP depends on receptor-mediated uptake of AVP in the kidney cells.


1977 ◽  
Vol 16 (03) ◽  
pp. 100-103 ◽  
Author(s):  
C. Schümichen ◽  
J. Waiden ◽  
G. Hoffmann

SummaryThe kinetic data of two different 99mTc-Sn-pyrophosphate compounds (compound A and B) were evaluated in non-adult rats. Only compound A concentrated in bone. Both compounds dispersed rapidly in the intravascular as well as the extravascular space. The plasma protein bond of both compounds increased with time after injection and impaired both the renal clearance of both compounds and the bone clearance of compound A. The renal clearance of both compounds was somewhat above that of 5 1Cr-EDTA. It is concluded that compound A and B is mainly excreted by glomerular filtration. About one fourth of the glomerular filtrate of compound B is reabsorbed and accumulated by the tubular cells.


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