scholarly journals Apparent Total Body Clearance Rate

2020 ◽  
Author(s):  
2009 ◽  
Vol 53 (8) ◽  
pp. 3266-3268 ◽  
Author(s):  
Kook-Hwan Oh ◽  
Chiweon Kim ◽  
Hankyu Lee ◽  
Hajeong Lee ◽  
Ji Yong Jung ◽  
...  

ABSTRACT The pharmacokinetic characteristics of piperacillin sodium were studied in five volunteers undergoing on-line hemodiafiltration (HDF). The subjects were given 2 g of piperacillin sodium intravenously over 1 min and placed on on-line HDF for 4 h starting at 60 min after the piperacillin infusion. Noncompartmental models were employed for estimation of the pharmacokinetic parameters, and intradialytic piperacillin clearance was calculated by the recovery method. The mean volume of distribution and the elimination half-life were 0.27 ± 0.13 liter/kg (mean ± standard deviation) and 1.1 ± 0.6 h, respectively. The total body clearance of piperacillin was 0.19 ± 0.08 liter/h/kg. Piperacillin clearance through on-line HDF was 0.11 ± 0.06 liter/h/kg. The mean serum piperacillin concentration was 4.0 ± 1.9 μg/ml at the end of the 4-h on-line HDF session. The concentration of infused piperacillin recovered in the dialysate was 527 ± 236 mg (26.3% ± 11.8%). We suggest the replacement of 500 mg of piperacillin after each on-line HDF session.


1995 ◽  
Vol 268 (4) ◽  
pp. R924-R930 ◽  
Author(s):  
A. Aneman ◽  
G. Eisenhofer ◽  
L. Fandriks ◽  
P. Friberg

Release and removal of norepinephrine (NE) by hepatomesenteric organs in anesthetized swine were examined using measurements of NE in arterial, portal, and hepatic venous plasma. NE spillover from the liver and mesenteric organs increased during splanchnic nerve stimulation, validating these measurements as indexes of sympathetic outflow. Administration of the neuronal uptake-blocking drug desipramine reduced mesenteric NE extraction more than hepatic extraction, suggesting that neuronal uptake was more important for NE removal in mesenteric organs than in the liver. Circulating NE was removed by the liver more efficiently than by mesenteric organs, whereas mesenteric NE spillover (2.46 nmol/min) exceeded liver NE spillover (0.74 nmol/min). Hepatomesenteric NE spillover represented 53% of total body spillover; NE clearance was 42% of total body clearance. Because of efficient hepatic extraction of NE released by mesenteric organs, the sum of mesenteric and hepatic NE spillovers (3.20 pmol/min) exceeded net hepatomesenteric spillover estimated using arterial and hepatic venous measurements alone (1.96 pmol/min). Thus valid assessment of the substantial amounts of NE released by hepatomesenteric organs requires separate examination of mesenteric and hepatic spillovers.


2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Alexandra Jacobs ◽  
Fabio Silvio Taccone ◽  
Jason A. Roberts ◽  
Frédérique Jacobs ◽  
Frederic Cotton ◽  
...  

ABSTRACTAugmented renal clearance is commonly observed in septic patients and may result in insufficient β-lactam serum concentrations. The aims of this study were to evaluate potential correlations between drug concentrations or total body clearance of β-lactam antibiotics and measured creatinine clearance and to quantify the need for drug dosage adjustments in septic patients with different levels of augmented renal clearance. We reviewed 256 antibiotic measurements (512 drug concentrations) from a cohort of 215 critically ill patients who had a measured creatinine clearance of ≥120 ml/min and who received therapeutic drug monitoring of meropenem, cefepime, ceftazidime, or piperacillin from October 2009 until December 2014 at Erasme Hospital. Population pharmacokinetic (PK) analysis of the data was performed using the Pmetrics software package for R. Fifty-five percent of drug concentrations showed insufficient β-lactam serum concentrations to treat infections due toPseudomonas aeruginosa. There were significant, yet weak, correlations between measured creatinine clearance and trough concentrations of meropenem (r= −0.21,P= 0.01), trough concentrations of piperacillin (r= −0.28,P= 0.0071), concentrations at 50% of the dosage interval (r= −0.41,P< 0.0001), and total body clearance of piperacillin (r= 0.39,P= 0.0002). Measured creatinine clearance adequately explained changes in drug concentrations in population pharmacokinetic models for cefepime, ceftazidime, and meropenem but not for piperacillin. Therefore, specific PK modeling can predict certain β-lactam concentrations based on renal function but not on absolute values of measured creatinine clearance, easily available for clinicians. Currently, routine therapeutic drug monitoring is required to adjust daily regimens in critically ill patients receiving standard dosing regimens.


1988 ◽  
Vol 6 (7) ◽  
pp. 1192-1196 ◽  
Author(s):  
S P Ackland ◽  
K E Choi ◽  
M J Ratain ◽  
M J Egorin ◽  
S F Williams ◽  
...  

Thiotepa is an established alkylating agent whose pharmacokinetics in standard doses are well defined. In order to ascertain whether dose-dependent variations in pharmacokinetics occur, we have undertaken an analysis of plasma thiotepa levels in 16 patients entered on a phase I-II study of bialkylator chemotherapy. High-dose thiotepa (1.8 to 7.0 mg/kg) and cyclophosphamide (2.5 g/m2) were administered intravenously (IV) on days -6, -4, and -2 followed by autologous marrow reinfusion on day 0. Plasma and urinary thiotepa was assayed by gas chromatography. Biexponential plasma decay curves were seen in ten patients, with a t 1/2 alpha of 10.0 +/- 6.4 minutes, a t 1/2 beta of 174 +/- 61 minutes and a total body clearance of 379 +/- 153 mL/h/kg (mean +/- SD). Six patients displayed monoexponential plasma decay curves with a terminal t 1/2 of 137 +/- 83 minutes and a total body clearance of 440 +/- 195 mL/h/kg. Although there was a trend toward reduced plasma clearance in the three patients treated at the highest dose level, the available data suggest that metabolic clearance mechanisms for thiotepa were not saturated with the doses used in this study. By stepwise regression analysis, linear functions using only 15-minute and four-hour postinfusion plasma levels were derived that correlated closely with area under the plasma concentration X time curves (AUC) (P less than .002). We conclude that high-dose thiotepa results in similar pharmacokinetic values to conventional doses with no apparent dose-dependent variation. The value of specific time points to predict AUC and clearance will require prospective evaluation.


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