Indinavir protein-free concentrations when used in indinavir/ritonavir combination therapy

Jennifer R. King, John G. Gerber, Courtney V. Fletcher, Lane Bushman, Edward P. Acosta

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Objective: To describe the in vivo protein-binding characteristics of indinavir (IDV) in the presence of ritonavir (RTV) relative to total IDV plasma concentrations. Design: The ACTG protocol 5055 was a multicenter study comparing the safety and pharmacokinetics of IDV/RTV at doses of 800/200 and 400/400 mg twice daily in HIV-infected adults. Methods: Forty-four patients underwent a 12-h intensive pharmacokinetic assessment after 2 weeks of therapy. Three plasma samples from 35 patients at Cmax, 6 and 12 h post dose were used to determine the unbound IDV concentrations. Unbound IDV was separated in plasma samples using ultra-filtration and measured using high-performance liquid chromatography with UV detection. Results: Mean IDV protein-bound fraction across all time points in the 800/200 and 400/400 arm were 53.4 and 51.8%, respectively. In the 800/200 arm, percentage binding at Cmax was 50% compared with 56% at 12 h (P = 0.008). In the 400/400 arm, percentage binding at Cmax was 49% compared with 54% at 12 h (P = 0.008). Conclusions: The extent of plasma protein binding of IDV in this study was less than in previously published data with IDV alone. Although IDV concentrations differed across the arms, the percentage of IDV protein binding at all time points was not different between the 800/200 and 400/400 arms. However, the percentage of IDV protein binding at Cmax was significantly lower compared with 12 h in each arm, possibly suggesting that IDV protein binding is concentration-dependent. These data suggest that RTV affects IDV protein-binding characteristics and IDV also exhibits concentration dependent binding when administered with RTV.

Original languageEnglish (US)
Pages (from-to)1059-1063
Number of pages5
JournalAIDS
Volume19
Issue number10
DOIs
StatePublished - Jul 1 2005

Fingerprint

Indinavir
Ritonavir
Protein Binding
Proteins
Therapeutics
Pharmacokinetics

Keywords

  • HIV/AIDS
  • Indinavir
  • Pharmacokinetics
  • Protein binding
  • Ritonavir

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Indinavir protein-free concentrations when used in indinavir/ritonavir combination therapy. / King, Jennifer R.; Gerber, John G.; Fletcher, Courtney V.; Bushman, Lane; Acosta, Edward P.

In: AIDS, Vol. 19, No. 10, 01.07.2005, p. 1059-1063.

Research output: Contribution to journalArticle

King, Jennifer R. ; Gerber, John G. ; Fletcher, Courtney V. ; Bushman, Lane ; Acosta, Edward P. / Indinavir protein-free concentrations when used in indinavir/ritonavir combination therapy. In: AIDS. 2005 ; Vol. 19, No. 10. pp. 1059-1063.
@article{79ebb50732aa421c911f9b00ffe39b92,
title = "Indinavir protein-free concentrations when used in indinavir/ritonavir combination therapy",
abstract = "Objective: To describe the in vivo protein-binding characteristics of indinavir (IDV) in the presence of ritonavir (RTV) relative to total IDV plasma concentrations. Design: The ACTG protocol 5055 was a multicenter study comparing the safety and pharmacokinetics of IDV/RTV at doses of 800/200 and 400/400 mg twice daily in HIV-infected adults. Methods: Forty-four patients underwent a 12-h intensive pharmacokinetic assessment after 2 weeks of therapy. Three plasma samples from 35 patients at Cmax, 6 and 12 h post dose were used to determine the unbound IDV concentrations. Unbound IDV was separated in plasma samples using ultra-filtration and measured using high-performance liquid chromatography with UV detection. Results: Mean IDV protein-bound fraction across all time points in the 800/200 and 400/400 arm were 53.4 and 51.8{\%}, respectively. In the 800/200 arm, percentage binding at Cmax was 50{\%} compared with 56{\%} at 12 h (P = 0.008). In the 400/400 arm, percentage binding at Cmax was 49{\%} compared with 54{\%} at 12 h (P = 0.008). Conclusions: The extent of plasma protein binding of IDV in this study was less than in previously published data with IDV alone. Although IDV concentrations differed across the arms, the percentage of IDV protein binding at all time points was not different between the 800/200 and 400/400 arms. However, the percentage of IDV protein binding at Cmax was significantly lower compared with 12 h in each arm, possibly suggesting that IDV protein binding is concentration-dependent. These data suggest that RTV affects IDV protein-binding characteristics and IDV also exhibits concentration dependent binding when administered with RTV.",
keywords = "HIV/AIDS, Indinavir, Pharmacokinetics, Protein binding, Ritonavir",
author = "King, {Jennifer R.} and Gerber, {John G.} and Fletcher, {Courtney V.} and Lane Bushman and Acosta, {Edward P.}",
year = "2005",
month = "7",
day = "1",
doi = "10.1097/01.aids.0000174452.78497.54",
language = "English (US)",
volume = "19",
pages = "1059--1063",
journal = "AIDS",
issn = "0269-9370",
publisher = "Lippincott Williams and Wilkins",
number = "10",

}

TY - JOUR

T1 - Indinavir protein-free concentrations when used in indinavir/ritonavir combination therapy

AU - King, Jennifer R.

AU - Gerber, John G.

AU - Fletcher, Courtney V.

AU - Bushman, Lane

AU - Acosta, Edward P.

PY - 2005/7/1

Y1 - 2005/7/1

N2 - Objective: To describe the in vivo protein-binding characteristics of indinavir (IDV) in the presence of ritonavir (RTV) relative to total IDV plasma concentrations. Design: The ACTG protocol 5055 was a multicenter study comparing the safety and pharmacokinetics of IDV/RTV at doses of 800/200 and 400/400 mg twice daily in HIV-infected adults. Methods: Forty-four patients underwent a 12-h intensive pharmacokinetic assessment after 2 weeks of therapy. Three plasma samples from 35 patients at Cmax, 6 and 12 h post dose were used to determine the unbound IDV concentrations. Unbound IDV was separated in plasma samples using ultra-filtration and measured using high-performance liquid chromatography with UV detection. Results: Mean IDV protein-bound fraction across all time points in the 800/200 and 400/400 arm were 53.4 and 51.8%, respectively. In the 800/200 arm, percentage binding at Cmax was 50% compared with 56% at 12 h (P = 0.008). In the 400/400 arm, percentage binding at Cmax was 49% compared with 54% at 12 h (P = 0.008). Conclusions: The extent of plasma protein binding of IDV in this study was less than in previously published data with IDV alone. Although IDV concentrations differed across the arms, the percentage of IDV protein binding at all time points was not different between the 800/200 and 400/400 arms. However, the percentage of IDV protein binding at Cmax was significantly lower compared with 12 h in each arm, possibly suggesting that IDV protein binding is concentration-dependent. These data suggest that RTV affects IDV protein-binding characteristics and IDV also exhibits concentration dependent binding when administered with RTV.

AB - Objective: To describe the in vivo protein-binding characteristics of indinavir (IDV) in the presence of ritonavir (RTV) relative to total IDV plasma concentrations. Design: The ACTG protocol 5055 was a multicenter study comparing the safety and pharmacokinetics of IDV/RTV at doses of 800/200 and 400/400 mg twice daily in HIV-infected adults. Methods: Forty-four patients underwent a 12-h intensive pharmacokinetic assessment after 2 weeks of therapy. Three plasma samples from 35 patients at Cmax, 6 and 12 h post dose were used to determine the unbound IDV concentrations. Unbound IDV was separated in plasma samples using ultra-filtration and measured using high-performance liquid chromatography with UV detection. Results: Mean IDV protein-bound fraction across all time points in the 800/200 and 400/400 arm were 53.4 and 51.8%, respectively. In the 800/200 arm, percentage binding at Cmax was 50% compared with 56% at 12 h (P = 0.008). In the 400/400 arm, percentage binding at Cmax was 49% compared with 54% at 12 h (P = 0.008). Conclusions: The extent of plasma protein binding of IDV in this study was less than in previously published data with IDV alone. Although IDV concentrations differed across the arms, the percentage of IDV protein binding at all time points was not different between the 800/200 and 400/400 arms. However, the percentage of IDV protein binding at Cmax was significantly lower compared with 12 h in each arm, possibly suggesting that IDV protein binding is concentration-dependent. These data suggest that RTV affects IDV protein-binding characteristics and IDV also exhibits concentration dependent binding when administered with RTV.

KW - HIV/AIDS

KW - Indinavir

KW - Pharmacokinetics

KW - Protein binding

KW - Ritonavir

UR - http://www.scopus.com/inward/record.url?scp=21844476813&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=21844476813&partnerID=8YFLogxK

U2 - 10.1097/01.aids.0000174452.78497.54

DO - 10.1097/01.aids.0000174452.78497.54

M3 - Article

C2 - 15958837

AN - SCOPUS:21844476813

VL - 19

SP - 1059

EP - 1063

JO - AIDS

JF - AIDS

SN - 0269-9370

IS - 10

ER -