Evaluation of an in vitro dialysis system to predict drug removal

Joanna Laizure, Thomas J. Comstock, George M. Feldman

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Background. Variation in the extent of drug removal under different dialysis conditions presents a challenge for prediction of drug elimination and dosage regimen adjustment during haemodialysis (HD). Dependence on clinical pharmacokinetic studies in HD patients for dosing guidelines is problematic given the increasing number of dialysers with variable rates of drug removal. Thus, the purpose of this study was to characterize drug removal using an in vitro system and to evaluate its reliability to predict in vivo elimination by HD using vancomycin (VANC) as a model drug. Methods. In vitro dialysis was performed for 2 h (volume 4.0 1 normal saline, initial VANC concentration 30mg/l, flow rate 300ml/min, dialysate flow 800 ml/min) using four different dialysers: polymethylmethacrylate (BK-2.1 U), polysulfone (F-80), AN69 (Filtral-20) and hemophan (COBE 700HE). The in vitro dialysis clearance for VANC (CL D) for the polysulfone dialyser was compared with values determined in eight HD patients. In vitro VANC CL D for all dialysers was compared with the clearance and KoA for B12 reported for each dialyser. Results. In vitro VANC CL D values were 93 ± 11 ml/min for the polymethylmethacrylate BK-2.1, 136 ± 7 ml/min for the AN69, 65 ± 9 ml/min for the hemophan COBE 700HE and 143 ± 10 ml/min for the polysulfone F80. The CL D for the polysulfone F80 was not statistically different from the in vivo CL D of 135 ± 18 ml/min (P = 0.48). In vitro VANC CL D correlated with the B12 CL D (r 2 = 0.77) and the B12 KoA (r 2 = 0.63) reported for each dialyser. Conclusion. VANC CL D in HD patients for the polysulfone dialyser was correctly predicted using the in vitro dialysis system. Use of this system may be superior to estimations of drug CL D based on dialyser information provided by the manufacturer for compounds of similar molecular weight.

Original languageEnglish (US)
Pages (from-to)400-405
Number of pages6
JournalNephrology Dialysis Transplantation
Volume19
Issue number2
DOIs
StatePublished - Feb 1 2004

Fingerprint

Vancomycin
Dialysis
Renal Dialysis
Pharmaceutical Preparations
Polymethyl Methacrylate
Dialysis Solutions
In Vitro Techniques
Pharmacokinetics
Molecular Weight
polysulfone P 1700
Guidelines

All Science Journal Classification (ASJC) codes

  • Nephrology
  • Transplantation

Cite this

Evaluation of an in vitro dialysis system to predict drug removal. / Laizure, Joanna; Comstock, Thomas J.; Feldman, George M.

In: Nephrology Dialysis Transplantation, Vol. 19, No. 2, 01.02.2004, p. 400-405.

Research output: Contribution to journalArticle

Laizure, Joanna ; Comstock, Thomas J. ; Feldman, George M. / Evaluation of an in vitro dialysis system to predict drug removal. In: Nephrology Dialysis Transplantation. 2004 ; Vol. 19, No. 2. pp. 400-405.
@article{d8af7b35181b4c2496eb41b22eb4a252,
title = "Evaluation of an in vitro dialysis system to predict drug removal",
abstract = "Background. Variation in the extent of drug removal under different dialysis conditions presents a challenge for prediction of drug elimination and dosage regimen adjustment during haemodialysis (HD). Dependence on clinical pharmacokinetic studies in HD patients for dosing guidelines is problematic given the increasing number of dialysers with variable rates of drug removal. Thus, the purpose of this study was to characterize drug removal using an in vitro system and to evaluate its reliability to predict in vivo elimination by HD using vancomycin (VANC) as a model drug. Methods. In vitro dialysis was performed for 2 h (volume 4.0 1 normal saline, initial VANC concentration 30mg/l, flow rate 300ml/min, dialysate flow 800 ml/min) using four different dialysers: polymethylmethacrylate (BK-2.1 U), polysulfone (F-80), AN69 (Filtral-20) and hemophan (COBE 700HE). The in vitro dialysis clearance for VANC (CL D) for the polysulfone dialyser was compared with values determined in eight HD patients. In vitro VANC CL D for all dialysers was compared with the clearance and KoA for B12 reported for each dialyser. Results. In vitro VANC CL D values were 93 ± 11 ml/min for the polymethylmethacrylate BK-2.1, 136 ± 7 ml/min for the AN69, 65 ± 9 ml/min for the hemophan COBE 700HE and 143 ± 10 ml/min for the polysulfone F80. The CL D for the polysulfone F80 was not statistically different from the in vivo CL D of 135 ± 18 ml/min (P = 0.48). In vitro VANC CL D correlated with the B12 CL D (r 2 = 0.77) and the B12 KoA (r 2 = 0.63) reported for each dialyser. Conclusion. VANC CL D in HD patients for the polysulfone dialyser was correctly predicted using the in vitro dialysis system. Use of this system may be superior to estimations of drug CL D based on dialyser information provided by the manufacturer for compounds of similar molecular weight.",
author = "Joanna Laizure and Comstock, {Thomas J.} and Feldman, {George M.}",
year = "2004",
month = "2",
day = "1",
doi = "10.1093/ndt/gfg550",
language = "English (US)",
volume = "19",
pages = "400--405",
journal = "Nephrology Dialysis Transplantation",
issn = "0931-0509",
publisher = "Oxford University Press",
number = "2",

}

TY - JOUR

T1 - Evaluation of an in vitro dialysis system to predict drug removal

AU - Laizure, Joanna

AU - Comstock, Thomas J.

AU - Feldman, George M.

PY - 2004/2/1

Y1 - 2004/2/1

N2 - Background. Variation in the extent of drug removal under different dialysis conditions presents a challenge for prediction of drug elimination and dosage regimen adjustment during haemodialysis (HD). Dependence on clinical pharmacokinetic studies in HD patients for dosing guidelines is problematic given the increasing number of dialysers with variable rates of drug removal. Thus, the purpose of this study was to characterize drug removal using an in vitro system and to evaluate its reliability to predict in vivo elimination by HD using vancomycin (VANC) as a model drug. Methods. In vitro dialysis was performed for 2 h (volume 4.0 1 normal saline, initial VANC concentration 30mg/l, flow rate 300ml/min, dialysate flow 800 ml/min) using four different dialysers: polymethylmethacrylate (BK-2.1 U), polysulfone (F-80), AN69 (Filtral-20) and hemophan (COBE 700HE). The in vitro dialysis clearance for VANC (CL D) for the polysulfone dialyser was compared with values determined in eight HD patients. In vitro VANC CL D for all dialysers was compared with the clearance and KoA for B12 reported for each dialyser. Results. In vitro VANC CL D values were 93 ± 11 ml/min for the polymethylmethacrylate BK-2.1, 136 ± 7 ml/min for the AN69, 65 ± 9 ml/min for the hemophan COBE 700HE and 143 ± 10 ml/min for the polysulfone F80. The CL D for the polysulfone F80 was not statistically different from the in vivo CL D of 135 ± 18 ml/min (P = 0.48). In vitro VANC CL D correlated with the B12 CL D (r 2 = 0.77) and the B12 KoA (r 2 = 0.63) reported for each dialyser. Conclusion. VANC CL D in HD patients for the polysulfone dialyser was correctly predicted using the in vitro dialysis system. Use of this system may be superior to estimations of drug CL D based on dialyser information provided by the manufacturer for compounds of similar molecular weight.

AB - Background. Variation in the extent of drug removal under different dialysis conditions presents a challenge for prediction of drug elimination and dosage regimen adjustment during haemodialysis (HD). Dependence on clinical pharmacokinetic studies in HD patients for dosing guidelines is problematic given the increasing number of dialysers with variable rates of drug removal. Thus, the purpose of this study was to characterize drug removal using an in vitro system and to evaluate its reliability to predict in vivo elimination by HD using vancomycin (VANC) as a model drug. Methods. In vitro dialysis was performed for 2 h (volume 4.0 1 normal saline, initial VANC concentration 30mg/l, flow rate 300ml/min, dialysate flow 800 ml/min) using four different dialysers: polymethylmethacrylate (BK-2.1 U), polysulfone (F-80), AN69 (Filtral-20) and hemophan (COBE 700HE). The in vitro dialysis clearance for VANC (CL D) for the polysulfone dialyser was compared with values determined in eight HD patients. In vitro VANC CL D for all dialysers was compared with the clearance and KoA for B12 reported for each dialyser. Results. In vitro VANC CL D values were 93 ± 11 ml/min for the polymethylmethacrylate BK-2.1, 136 ± 7 ml/min for the AN69, 65 ± 9 ml/min for the hemophan COBE 700HE and 143 ± 10 ml/min for the polysulfone F80. The CL D for the polysulfone F80 was not statistically different from the in vivo CL D of 135 ± 18 ml/min (P = 0.48). In vitro VANC CL D correlated with the B12 CL D (r 2 = 0.77) and the B12 KoA (r 2 = 0.63) reported for each dialyser. Conclusion. VANC CL D in HD patients for the polysulfone dialyser was correctly predicted using the in vitro dialysis system. Use of this system may be superior to estimations of drug CL D based on dialyser information provided by the manufacturer for compounds of similar molecular weight.

UR - http://www.scopus.com/inward/record.url?scp=1042292025&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=1042292025&partnerID=8YFLogxK

U2 - 10.1093/ndt/gfg550

DO - 10.1093/ndt/gfg550

M3 - Article

C2 - 14736965

AN - SCOPUS:1042292025

VL - 19

SP - 400

EP - 405

JO - Nephrology Dialysis Transplantation

JF - Nephrology Dialysis Transplantation

SN - 0931-0509

IS - 2

ER -