Tedizolid Adsorption and Transmembrane Clearance during in vitro Continuous Renal Replacement Therapy

2015 ◽  
Vol 40 (1) ◽  
pp. 66-71 ◽  
Author(s):  
Susan J. Lewis ◽  
Lynn A. Switaj ◽  
Bruce A. Mueller
Keyword(s):  
Renal Replacement Therapy ◽  
Clinical Setting ◽  
Total Body Clearance ◽  
Irreversible Adsorption ◽  
Continuous Hemofiltration ◽  
Total Body ◽  
Require Dose ◽  
Continuous Hemodialysis ◽  
Body Clearance

Background/Aims: To study transmembrane clearance (CLTM) and adsorption of tedizolid, a novel oxazolidinone antibiotic, in continuous hemofiltration (CVVH) and continuous hemodialysis (CVVHD). Methods: In vitro CVVH/CVVHD models with polysulfone and AN69 hemodiafilters were used. Tedizolid CLTM during CVVH/CVVHD was assessed at various ultrafiltrate (Quf) and dialysate rates (Qd). Tedizolid adsorption was tested in a recirculating CVVH model over 4 h. Results: In CVVH, CLTM did not differ between filter types. In CVVHD, tedizolid CLTM was significantly higher with the polysulfone hemodiafilter at Qd 6 l/h (p < 0.02). Tedizolid exhibited irreversible adsorption to the CRRT apparatus and bound significantly higher to the polysulfone hemodiafilter. Conclusion: Tedizolid's CLTM is dependent on Qd, Quf, and hemodiafilter type. At conventional CRRT rates, tedizolid CLTM appears modest relative to total body clearance and is unlikely to require dose adjustments. CRRT adsorption in the clinical setting is likely less than what we observed in this in vitro, continuously recirculating blood model.

Pharmacokinetics of ceftriaxone in patients undergoing continuous renal replacement therapy

2016 ◽  
Vol 27 (6) ◽  
Author(s):  
Koji Goto ◽  
Yuhki Sato ◽  
Norihisa Yasuda ◽  
Seigo Hidaka ◽  
Yosuke Suzuki ◽  
...  
Keyword(s):  
Renal Replacement Therapy ◽  
Continuous Renal Replacement Therapy ◽  
Replacement Therapy ◽  
High Performance ◽  
Total Body Clearance ◽  
Dose Interval ◽  
Serum Levels ◽  
Filtration Fraction ◽  
Total Body ◽  
Body Clearance

AbstractBackground:The duration of time for which the serum levels exceed the minimum inhibitory concentration (MIC) is an important pharmacokinetics (PK)/pharmacodynamics (PD) parameter correlating with efficacy for the antibiotic, ceftriaxone (CTRX). However, no reports exist regarding the PK or PD in patients undergoing continuous renal replacement therapy (CRRT). The purpose of this study was to examine the PK and safety of CTRX in patients undergoing CRRT in order to establish safer and more effective regimens.Methods:CTRX (1 g once a day) was intravenously administered four or more times to nine patients undergoing CRRT. Blood was collected after administration to measure CTRX concentrations in serum and the filtration fraction of CRRT by high-performance liquid chromatography. In addition to calculating PK parameters from serum CTRX, we (a) estimated by simulation CTRX concentrations when the dose interval was extended to once every 2 or 3 days, (b) calculated CTRX clearance via CRRT from CTRX concentrations in the filtration fraction, and (c) assessed the safety of CTRX use.Results:Total body clearance and the half-life of CTRX were 7.46 mL/min (mean) and 26.5 h, respectively, in patients undergoing CRRT. CTRX was found in the filtration fraction, and the estimated clearance by CRRT was about 70% of total body clearance. Simulations revealed that even when the dose interval is increased to 2 or 3 days, CTRX would retain its efficacy.Conclusions:Our findings suggest that, depending on the condition of patients undergoing CRRT, CTRX could be used safely against pathogens with a CTRX MIC ≤2 µg/mL, even when extending the dose interval.

Combined Boric Acid and Cinchocaine Chloride Poisoning in a 12-month-old Infant: Evaluation of Haemodialysis

1988 ◽  
Vol 7 (2) ◽  
pp. 175-178 ◽  
Author(s):  
M. Egfjord ◽  
J.A. Jansen ◽  
H. Flachs ◽  
J.S. Schou
Keyword(s):  
Renal Function ◽  
Boric Acid ◽  
Half Life ◽  
Total Body Clearance ◽  
Renal Toxicity ◽  
Chloride Poisoning ◽  
Total Body ◽  
Plasma Half Life ◽  
Body Clearance

A mixture containing 3 g of boric acid and 300 mg of cinchocaine chloride prescribed due to painful dental protrusion was accidentally ingested by a 12-month-old girl. She developed violent vomiting and coughing. Irritability, tremor, seizures and a delirious reaction. She was treated with diazepam, intubated, sedated and ventilated. Her diuresis was stimulated with furosemide and fluid. Within the first 24 h she was treated with haemodialysis twice on femoral catheters. Her renal function was unaffected. In two days she fully recovered. The maximum measured levels of boric acid and cinchocaine chloride approximately 6 h after ingestion were 26 μg/ml and 71 ng/ml respectively. The plasma half-life of boric acid was 7.0 h and decreased to 3.6 and 4.4 h during the two haemodialyses. The total body clearance of boric acid increased correspondingly from 21 ml/min to 41 and 34 ml/min. The in vitro clearance of boric acid of the dialyser was later determined to be 18 ml/min. It is concluded that haemodialysis is valuable in the treatment of boric acid intoxication because it increases the elimination of the drug even in patients without any sign of renal toxicity.

Human Kidneys Play an Important Role in the Elimination of Propofol

2005 ◽  
Vol 102 (2) ◽  
pp. 327-330 ◽  
Author(s):  
Daisuke Takizawa ◽  
Haruhiko Hiraoka ◽  
Fumio Goto ◽  
Koujirou Yamamoto ◽  
Ryuya Horiuchi
Keyword(s):  
Blood Flow ◽  
Nitrous Oxide ◽  
Total Body Clearance ◽  
Arterial Blood ◽  
Venous Sample ◽  
Total Body ◽  
Body Clearance ◽  
Arterial Sample

Background Extrahepatic clearance of propofol has been suggested because its total body clearance exceeds hepatic blood flow. However, it remains uncertain which organs are involved in the extrahepatic clearance of propofol. In vitro studies suggest that the kidneys contribute to the clearance of this drug. The purpose of this study was to confirm whether human kidneys participate in propofol disposition in vivo. Methods Ten patients scheduled to undergo nephrectomy were enrolled in this study. Renal blood flow was measured using para-aminohippurate. Anesthesia was induced with vecuronium (0.1 mg/kg) and propofol (2 mg/kg) and then maintained with nitrous oxide (60%), sevoflurane (1 approximately 2%) in oxygen, and an infusion of propofol (2 mg . kg . h). Radial arterial blood for propofol and para-aminohippurate analysis was collected from a cannula inserted in the radial artery. The renal venous sample and the radial arterial sample were obtained at the same time after the steady state of propofol was established. Results The renal extraction ratio of propofol was 0.58 +/- 0.15 (mean +/- SD). The renal clearance of propofol was 0.41 +/- 0.15 l/min (mean +/- SD), or 27 +/- 9.9% (mean +/- SD) of total body clearance. Conclusion Human kidneys play an important role in the elimination of propofol.

scholarly journals Pharmacokinetics of Intravenous Piperacillin Administration in Patients Undergoing On-Line Hemodiafiltration

2009 ◽  
Vol 53 (8) ◽  
pp. 3266-3268 ◽  
Author(s):  
Kook-Hwan Oh ◽  
Chiweon Kim ◽  
Hankyu Lee ◽  
Hajeong Lee ◽  
Ji Yong Jung ◽  
...  
Keyword(s):  
Standard Deviation ◽  
Total Body Clearance ◽  
Volume Of Distribution ◽  
Pharmacokinetic Parameters ◽  
Recovery Method ◽  
Elimination Half ◽  
On Line ◽  
The Mean ◽  
Total Body ◽  
Body Clearance

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.

Hepatomesenteric release and removal of norepinephrine in swine

1995 ◽  
Vol 268 (4) ◽  
pp. R924-R930 ◽  
Author(s):  
A. Aneman ◽  
G. Eisenhofer ◽  
L. Fandriks ◽  
P. Friberg
Keyword(s):  
Total Body Clearance ◽  
Splanchnic Nerve ◽  
Neuronal Uptake ◽  
Blocking Drug ◽  
Hepatic Extraction ◽  
Valid Assessment ◽  
Total Body ◽  
Splanchnic Nerve Stimulation ◽  
Body Clearance ◽  
Venous Plasma

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.

scholarly journals β-Lactam Dosage Regimens in Septic Patients with Augmented Renal Clearance

2018 ◽  
Vol 62 (9) ◽  
Author(s):  
Alexandra Jacobs ◽  
Fabio Silvio Taccone ◽  
Jason A. Roberts ◽  
Frédérique Jacobs ◽  
Frederic Cotton ◽  
...  
Keyword(s):  
Creatinine Clearance ◽  
Renal Clearance ◽  
Total Body Clearance ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic ◽  
Augmented Renal Clearance ◽  
Drug Concentrations ◽  
Trough Concentrations ◽  
Total Body ◽  
Body Clearance

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.

Human plasma pharmacokinetics of thiotepa following administration of high-dose thiotepa and cyclophosphamide.

1988 ◽  
Vol 6 (7) ◽  
pp. 1192-1196 ◽  
Author(s):  
S P Ackland ◽  
K E Choi ◽  
M J Ratain ◽  
M J Egorin ◽  
S F Williams ◽  
...  
Keyword(s):  
Stepwise Regression ◽  
Total Body Clearance ◽  
Linear Functions ◽  
High Dose ◽  
Metabolic Clearance ◽  
Plasma Decay ◽  
Plasma Pharmacokinetics ◽  
Total Body ◽  
Dose Dependent ◽  
Body Clearance

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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