Comparison of fitting methods for the analysis of plasma concentration-time data resulting from constant rate intravenous infusion

S. L. Johnson, Michael Mayersohn

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Plasma concentration-time data resulting from constant rate intravenous infusion may be analysed in two ways: 1. Samples may be collected both during and after infusion and fit to an infusion model. 2. Samples may be collected after infusion is complete and the data may be fit as an i.v. bolus. The purpose of this study was to contrast the two fitting procedures in terms of the accuracy of the parameter values obtained. Concentration-time data were computer-generated with the introduction of random error to simulate the disposition profiles of two model drugs. The results of these simulations indicate that satisfactory values for area-dependent parameters may be obtained without fitting data during the infusion phase. The exception to this is the apparent steady-state volume whose values become less accurate with longer infusion times. The parameters most affected by ignoring data points in the infusion phase are the central volume of distribution, and the coefficient and disposition rate constant associated with the initial, rapid phase of disposition. The equation which describes the entire concentration-time profile provides the most accurate parameter estimates of the model equation. In addition, we also describe the influence of the fitting method on the intercompartmental transfer rate constants.

Original languageEnglish (US)
Pages (from-to)313-323
Number of pages11
JournalBiopharmaceutics and Drug Disposition
Volume6
Issue number3
StatePublished - 1985

Fingerprint

Intravenous Infusions
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

@article{bf849ac7534642b1994600ab71675122,
title = "Comparison of fitting methods for the analysis of plasma concentration-time data resulting from constant rate intravenous infusion",
abstract = "Plasma concentration-time data resulting from constant rate intravenous infusion may be analysed in two ways: 1. Samples may be collected both during and after infusion and fit to an infusion model. 2. Samples may be collected after infusion is complete and the data may be fit as an i.v. bolus. The purpose of this study was to contrast the two fitting procedures in terms of the accuracy of the parameter values obtained. Concentration-time data were computer-generated with the introduction of random error to simulate the disposition profiles of two model drugs. The results of these simulations indicate that satisfactory values for area-dependent parameters may be obtained without fitting data during the infusion phase. The exception to this is the apparent steady-state volume whose values become less accurate with longer infusion times. The parameters most affected by ignoring data points in the infusion phase are the central volume of distribution, and the coefficient and disposition rate constant associated with the initial, rapid phase of disposition. The equation which describes the entire concentration-time profile provides the most accurate parameter estimates of the model equation. In addition, we also describe the influence of the fitting method on the intercompartmental transfer rate constants.",
author = "Johnson, {S. L.} and Michael Mayersohn",
year = "1985",
language = "English (US)",
volume = "6",
pages = "313--323",
journal = "Biopharmaceutics and Drug Disposition",
issn = "0142-2782",
publisher = "John Wiley and Sons Ltd",
number = "3",

}

TY - JOUR

T1 - Comparison of fitting methods for the analysis of plasma concentration-time data resulting from constant rate intravenous infusion

AU - Johnson, S. L.

AU - Mayersohn, Michael

PY - 1985

Y1 - 1985

N2 - Plasma concentration-time data resulting from constant rate intravenous infusion may be analysed in two ways: 1. Samples may be collected both during and after infusion and fit to an infusion model. 2. Samples may be collected after infusion is complete and the data may be fit as an i.v. bolus. The purpose of this study was to contrast the two fitting procedures in terms of the accuracy of the parameter values obtained. Concentration-time data were computer-generated with the introduction of random error to simulate the disposition profiles of two model drugs. The results of these simulations indicate that satisfactory values for area-dependent parameters may be obtained without fitting data during the infusion phase. The exception to this is the apparent steady-state volume whose values become less accurate with longer infusion times. The parameters most affected by ignoring data points in the infusion phase are the central volume of distribution, and the coefficient and disposition rate constant associated with the initial, rapid phase of disposition. The equation which describes the entire concentration-time profile provides the most accurate parameter estimates of the model equation. In addition, we also describe the influence of the fitting method on the intercompartmental transfer rate constants.

AB - Plasma concentration-time data resulting from constant rate intravenous infusion may be analysed in two ways: 1. Samples may be collected both during and after infusion and fit to an infusion model. 2. Samples may be collected after infusion is complete and the data may be fit as an i.v. bolus. The purpose of this study was to contrast the two fitting procedures in terms of the accuracy of the parameter values obtained. Concentration-time data were computer-generated with the introduction of random error to simulate the disposition profiles of two model drugs. The results of these simulations indicate that satisfactory values for area-dependent parameters may be obtained without fitting data during the infusion phase. The exception to this is the apparent steady-state volume whose values become less accurate with longer infusion times. The parameters most affected by ignoring data points in the infusion phase are the central volume of distribution, and the coefficient and disposition rate constant associated with the initial, rapid phase of disposition. The equation which describes the entire concentration-time profile provides the most accurate parameter estimates of the model equation. In addition, we also describe the influence of the fitting method on the intercompartmental transfer rate constants.

UR - http://www.scopus.com/inward/record.url?scp=0021879238&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0021879238&partnerID=8YFLogxK

M3 - Article

C2 - 4041557

AN - SCOPUS:0021879238

VL - 6

SP - 313

EP - 323

JO - Biopharmaceutics and Drug Disposition

JF - Biopharmaceutics and Drug Disposition

SN - 0142-2782

IS - 3

ER -