Prediction of precipitation-induced phlebitis: A statistical validation of an in vitro model

Jennifer L H Johnson, Yan He, Samuel H Yalkowsky

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

To avoid phlebitis, new intravenous (IV) parenterals are often screened by injection into animals. This method is not only expensive and time consuming, it is also detrimental to the animals. An alternate method, focusing on precipitation as the cause, uses an in vitro dynamic injection model that requires less money and time and reduces the need for live models. Validation of the dynamic injection apparatus, for predicting mechanical phlebitis, is established. Twenty-one currently marketed IV products were injected into isotonic Sorenson's phosphate buffer flowing at 5 mL/min. The resulting opacities, produced by precipitation, are measured in an ultraviolet flow cell. These opacity data, coupled with literature reports on phlebitis occurrence, were used to generate a logistic regression that indicates the probability of phlebitis given an opacity value measured by the apparatus. Regression results are supported by a receiver operator characteristic curve that establishes the most ideal cut-off opacity value. This opacity value provides the highest combined sensitivity (statistical power) and specificity while minimizing false-positive and false-negative results. Both analyses show that an opacity value of 0.003 best delineates phlebitic and nonphlebitic products. Measures of sensitivity (0.83), specificity (0.93), positive predictive value (0.93), and negative predictive value (0.78) indicate the model's predictive accuracy and reliability. These results support the use of the dynamic model in place of animals for preliminary phlebitis testing of new IV injectables.

Original languageEnglish (US)
Pages (from-to)1574-1581
Number of pages8
JournalJournal of Pharmaceutical Sciences
Volume92
Issue number8
DOIs
StatePublished - Aug 1 2003

Fingerprint

Phlebitis
Opacity
Injections
Animals
Buffers
Logistic Models
Phosphates
In Vitro Techniques
Logistics
Dynamic models
Sensitivity and Specificity
Testing

Keywords

  • In vitro model
  • Intravenous
  • Phlebitis
  • Precipitation
  • Validation

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science

Cite this

Prediction of precipitation-induced phlebitis : A statistical validation of an in vitro model. / Johnson, Jennifer L H; He, Yan; Yalkowsky, Samuel H.

In: Journal of Pharmaceutical Sciences, Vol. 92, No. 8, 01.08.2003, p. 1574-1581.

Research output: Contribution to journalArticle

@article{351dd6e1634e468085d27f64d32cbd5c,
title = "Prediction of precipitation-induced phlebitis: A statistical validation of an in vitro model",
abstract = "To avoid phlebitis, new intravenous (IV) parenterals are often screened by injection into animals. This method is not only expensive and time consuming, it is also detrimental to the animals. An alternate method, focusing on precipitation as the cause, uses an in vitro dynamic injection model that requires less money and time and reduces the need for live models. Validation of the dynamic injection apparatus, for predicting mechanical phlebitis, is established. Twenty-one currently marketed IV products were injected into isotonic Sorenson's phosphate buffer flowing at 5 mL/min. The resulting opacities, produced by precipitation, are measured in an ultraviolet flow cell. These opacity data, coupled with literature reports on phlebitis occurrence, were used to generate a logistic regression that indicates the probability of phlebitis given an opacity value measured by the apparatus. Regression results are supported by a receiver operator characteristic curve that establishes the most ideal cut-off opacity value. This opacity value provides the highest combined sensitivity (statistical power) and specificity while minimizing false-positive and false-negative results. Both analyses show that an opacity value of 0.003 best delineates phlebitic and nonphlebitic products. Measures of sensitivity (0.83), specificity (0.93), positive predictive value (0.93), and negative predictive value (0.78) indicate the model's predictive accuracy and reliability. These results support the use of the dynamic model in place of animals for preliminary phlebitis testing of new IV injectables.",
keywords = "In vitro model, Intravenous, Phlebitis, Precipitation, Validation",
author = "Johnson, {Jennifer L H} and Yan He and Yalkowsky, {Samuel H}",
year = "2003",
month = "8",
day = "1",
doi = "10.1002/jps.10396",
language = "English (US)",
volume = "92",
pages = "1574--1581",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "John Wiley and Sons Inc.",
number = "8",

}

TY - JOUR

T1 - Prediction of precipitation-induced phlebitis

T2 - A statistical validation of an in vitro model

AU - Johnson, Jennifer L H

AU - He, Yan

AU - Yalkowsky, Samuel H

PY - 2003/8/1

Y1 - 2003/8/1

N2 - To avoid phlebitis, new intravenous (IV) parenterals are often screened by injection into animals. This method is not only expensive and time consuming, it is also detrimental to the animals. An alternate method, focusing on precipitation as the cause, uses an in vitro dynamic injection model that requires less money and time and reduces the need for live models. Validation of the dynamic injection apparatus, for predicting mechanical phlebitis, is established. Twenty-one currently marketed IV products were injected into isotonic Sorenson's phosphate buffer flowing at 5 mL/min. The resulting opacities, produced by precipitation, are measured in an ultraviolet flow cell. These opacity data, coupled with literature reports on phlebitis occurrence, were used to generate a logistic regression that indicates the probability of phlebitis given an opacity value measured by the apparatus. Regression results are supported by a receiver operator characteristic curve that establishes the most ideal cut-off opacity value. This opacity value provides the highest combined sensitivity (statistical power) and specificity while minimizing false-positive and false-negative results. Both analyses show that an opacity value of 0.003 best delineates phlebitic and nonphlebitic products. Measures of sensitivity (0.83), specificity (0.93), positive predictive value (0.93), and negative predictive value (0.78) indicate the model's predictive accuracy and reliability. These results support the use of the dynamic model in place of animals for preliminary phlebitis testing of new IV injectables.

AB - To avoid phlebitis, new intravenous (IV) parenterals are often screened by injection into animals. This method is not only expensive and time consuming, it is also detrimental to the animals. An alternate method, focusing on precipitation as the cause, uses an in vitro dynamic injection model that requires less money and time and reduces the need for live models. Validation of the dynamic injection apparatus, for predicting mechanical phlebitis, is established. Twenty-one currently marketed IV products were injected into isotonic Sorenson's phosphate buffer flowing at 5 mL/min. The resulting opacities, produced by precipitation, are measured in an ultraviolet flow cell. These opacity data, coupled with literature reports on phlebitis occurrence, were used to generate a logistic regression that indicates the probability of phlebitis given an opacity value measured by the apparatus. Regression results are supported by a receiver operator characteristic curve that establishes the most ideal cut-off opacity value. This opacity value provides the highest combined sensitivity (statistical power) and specificity while minimizing false-positive and false-negative results. Both analyses show that an opacity value of 0.003 best delineates phlebitic and nonphlebitic products. Measures of sensitivity (0.83), specificity (0.93), positive predictive value (0.93), and negative predictive value (0.78) indicate the model's predictive accuracy and reliability. These results support the use of the dynamic model in place of animals for preliminary phlebitis testing of new IV injectables.

KW - In vitro model

KW - Intravenous

KW - Phlebitis

KW - Precipitation

KW - Validation

UR - http://www.scopus.com/inward/record.url?scp=0043212022&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0043212022&partnerID=8YFLogxK

U2 - 10.1002/jps.10396

DO - 10.1002/jps.10396

M3 - Article

C2 - 12884244

AN - SCOPUS:0043212022

VL - 92

SP - 1574

EP - 1581

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 8

ER -