schliessen

Filtern

 

Bibliotheken

Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047

Lipid lowering therapy is used increasingly in persons with HIV infection in the absence of safety data or information on drug interactions with antiretroviral agents. The primary objectives of this study were to examine the effects of ritonavir (RTV) plus saquinavir soft-gel (SQVsgc) capsules on th... Full description

Journal Title: AIDS (London) 2002, Vol.16 (4), p.569-577
Main Author: FICHTENBAUM, Carl J
Other Authors: GERBER, John G , ROSENKRANZ, Susan L , SEGAL, Yoninah , ABERG, Judith A , BLASCHKE, Terrence , ALSTON, Beverly , FANG FANG , KOSEL, Bradley , AWEEKA, Francesca
Format: Electronic Article Electronic Article
Language: English
Subjects:
Publisher: Hagerstown, MD: Lippincott Williams & Wilkins
ID: ISSN: 0269-9370
Zum Text:
SendSend as email Add to Book BagAdd to Book Bag
Staff View
recordid: cdi_proquest_miscellaneous_18321811
title: Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047
format: Article
creator:
  • FICHTENBAUM, Carl J
  • GERBER, John G
  • ROSENKRANZ, Susan L
  • SEGAL, Yoninah
  • ABERG, Judith A
  • BLASCHKE, Terrence
  • ALSTON, Beverly
  • FANG FANG
  • KOSEL, Bradley
  • AWEEKA, Francesca
subjects:
  • Adult
  • Antibiotics. Antiinfectious agents. Antiparasitic agents
  • Anticholesteremic Agents - adverse effects
  • Anticholesteremic Agents - pharmacokinetics
  • Antiviral agents
  • Atorvastatin
  • Biological and medical sciences
  • Drug Interactions
  • Heptanoic Acids - adverse effects
  • Heptanoic Acids - pharmacokinetics
  • HIV Protease Inhibitors - pharmacokinetics
  • HIV Seronegativity
  • Human Experimentation
  • Human immunodeficiency virus
  • Human viral diseases
  • Humans
  • Infectious diseases
  • Medical sciences
  • Pharmacology. Drug treatments
  • pravastatin
  • Pravastatin - adverse effects
  • Pravastatin - pharmacokinetics
  • Pyrroles - adverse effects
  • Pyrroles - pharmacokinetics
  • Ritonavir - pharmacokinetics
  • Saquinavir - pharmacokinetics
  • simvastatin
  • Simvastatin - adverse effects
  • Simvastatin - pharmacokinetics
  • Viral diseases
  • Viral diseases of the lymphoid tissue and the blood. Aids
ispartof: AIDS (London), 2002, Vol.16 (4), p.569-577
description: Lipid lowering therapy is used increasingly in persons with HIV infection in the absence of safety data or information on drug interactions with antiretroviral agents. The primary objectives of this study were to examine the effects of ritonavir (RTV) plus saquinavir soft-gel (SQVsgc) capsules on the pharmacokinetics of pravastatin, simvastatin, and atorvastatin, and the effect of pravastatin on the pharmacokinetics of nelfinavir (NFV) in order to determine clinically important drug-drug interactions. Randomized, open-label study in healthy, HIV seronegative adults at AIDS Clinical Trials Units across the USA. Three groups of subjects (arms 1, 2, and 3) received pravastatin, simvastatin or atorvastatin (40 mg daily each) from days 1-4 and 15-18. In these groups, RTV 400 mg and SQVsgc 400 mg twice daily were given from days 4-18. A fourth group (arm 4) received NFV 1250 mg twice daily from days 1-14 with pravastatin 40 mg daily added from days 15-18. Statin and NFV levels were measured by liquid chromatography/tandem mass spectrometry. Fifty-six subjects completed both pharmacokinetic study days. In arms 1-3, the median estimated area under the curves (AUC)(0-24) for the statins were: pravastatin (arm 1, n = 13), 151 and 75 ng.h/ml on days 4 and 18 (decline of 50% in presence of RTV/SQVsgc), respectively (P = 0.005); simvastatin (arm 2, n = 14), 17 and 548 ng.h/ml on days 4 and 18 (increase of 3059% in the presence of RTV/SQVsgc), respectively (P < 0.001); and total active atorvastatin (arm 3, n = 14), 167 and 289 ng.h/ml on days 4 and 18 (increase of 79% in the presence of RTV/SQVsgc), respectively (P < 0.001). In arm 4, the median estimated AUC(0-8) for NFV (24 319 versus 26 760 ng.h/ml; P = 0.58) and its active M8 metabolite (15 565 versus 14 571 ng.h/m; P = 0.63) were not statistically different from day 14 to day 18 (without or with pravastatin). Simvastatin should be avoided and atorvastatin may be used with caution in persons taking RTV and SQVsgc. Dose adjustment of pravastatin may be necessary with concomitant use of RTV and SQVsgc. Pravastatin does not alter the NFV pharmacokinetics, and thus appears to be safe for concomitant use.
language: eng
source:
identifier: ISSN: 0269-9370
fulltext: no_fulltext
issn:
  • 0269-9370
  • 1473-5571
url: Link


@attributes
NO1
SEARCH_ENGINEprimo_central_multiple_fe
SEARCH_ENGINE_TYPEPrimo Central Search Engine
RANK2.456752
LOCALfalse
PrimoNMBib
record
control
sourceidproquest_cross
recordidTN_cdi_proquest_miscellaneous_18321811
sourceformatXML
sourcesystemPC
sourcerecordid18321811
originalsourceidFETCH-LOGICAL-1420t-667c75cfa0031f558a5cfd054f09a719da200a8fca7483c667e8001433263ff00
addsrcrecordideNqFkE1v1DAQhi0EokvhLyBf4BYYx3HscEBaraCtVAkkCtdo1hlTQ9YutlPUf4-XXajEBV9G8_qZr5cxLuCVgEG_hvpakNC0h2ig2UvmAVuJTstGKS0eshW0_dAMUsMJe5Lzt0ooMOYxOxHCaFnTFVs-XmPaoY3ffaDiLfehUEJbfAyZb6n8JAr8JsVCmKn-XvutLzFljmHiuWDxlfOBn1984ZlSDPS1arfEb-O81F6U8hu-3lyd8U9lme74WkGnn7JHDudMz47xlH1-_-5qc95cfji72KwvG9G1UJq-11Yr6xBACqeUwZpMoDoHA2oxTFjvR-Ms6s5IW3EyAKKTsu2lcwCn7OWhbz3gx0K5jDufLc0zBopLHoWRrTBCVNAcQJtizonceJP8DtPdKGDcWz7-sXz8a_lvydTS58cZy3ZH033h0eMKvDgCmC3OLmGwPt9zUnW96dvKvf1nB-v3_sZQEvr5_5v8Aj3am1s
sourcetypeAggregation Database
isCDItrue
recordtypearticle
pqid18321811
display
typearticle
titlePharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047
creatorFICHTENBAUM, Carl J ; GERBER, John G ; ROSENKRANZ, Susan L ; SEGAL, Yoninah ; ABERG, Judith A ; BLASCHKE, Terrence ; ALSTON, Beverly ; FANG FANG ; KOSEL, Bradley ; AWEEKA, Francesca
creatorcontribFICHTENBAUM, Carl J ; GERBER, John G ; ROSENKRANZ, Susan L ; SEGAL, Yoninah ; ABERG, Judith A ; BLASCHKE, Terrence ; ALSTON, Beverly ; FANG FANG ; KOSEL, Bradley ; AWEEKA, Francesca ; NIAID AIDS Clinical Trials Group
descriptionLipid lowering therapy is used increasingly in persons with HIV infection in the absence of safety data or information on drug interactions with antiretroviral agents. The primary objectives of this study were to examine the effects of ritonavir (RTV) plus saquinavir soft-gel (SQVsgc) capsules on the pharmacokinetics of pravastatin, simvastatin, and atorvastatin, and the effect of pravastatin on the pharmacokinetics of nelfinavir (NFV) in order to determine clinically important drug-drug interactions. Randomized, open-label study in healthy, HIV seronegative adults at AIDS Clinical Trials Units across the USA. Three groups of subjects (arms 1, 2, and 3) received pravastatin, simvastatin or atorvastatin (40 mg daily each) from days 1-4 and 15-18. In these groups, RTV 400 mg and SQVsgc 400 mg twice daily were given from days 4-18. A fourth group (arm 4) received NFV 1250 mg twice daily from days 1-14 with pravastatin 40 mg daily added from days 15-18. Statin and NFV levels were measured by liquid chromatography/tandem mass spectrometry. Fifty-six subjects completed both pharmacokinetic study days. In arms 1-3, the median estimated area under the curves (AUC)(0-24) for the statins were: pravastatin (arm 1, n = 13), 151 and 75 ng.h/ml on days 4 and 18 (decline of 50% in presence of RTV/SQVsgc), respectively (P = 0.005); simvastatin (arm 2, n = 14), 17 and 548 ng.h/ml on days 4 and 18 (increase of 3059% in the presence of RTV/SQVsgc), respectively (P < 0.001); and total active atorvastatin (arm 3, n = 14), 167 and 289 ng.h/ml on days 4 and 18 (increase of 79% in the presence of RTV/SQVsgc), respectively (P < 0.001). In arm 4, the median estimated AUC(0-8) for NFV (24 319 versus 26 760 ng.h/ml; P = 0.58) and its active M8 metabolite (15 565 versus 14 571 ng.h/m; P = 0.63) were not statistically different from day 14 to day 18 (without or with pravastatin). Simvastatin should be avoided and atorvastatin may be used with caution in persons taking RTV and SQVsgc. Dose adjustment of pravastatin may be necessary with concomitant use of RTV and SQVsgc. Pravastatin does not alter the NFV pharmacokinetics, and thus appears to be safe for concomitant use.
identifier
0ISSN: 0269-9370
1EISSN: 1473-5571
2DOI: 10.1097/00002030-200203080-00008
3PMID: 11873000
languageeng
publisherHagerstown, MD: Lippincott Williams & Wilkins
subjectAdult ; Antibiotics. Antiinfectious agents. Antiparasitic agents ; Anticholesteremic Agents - adverse effects ; Anticholesteremic Agents - pharmacokinetics ; Antiviral agents ; Atorvastatin ; Biological and medical sciences ; Drug Interactions ; Heptanoic Acids - adverse effects ; Heptanoic Acids - pharmacokinetics ; HIV Protease Inhibitors - pharmacokinetics ; HIV Seronegativity ; Human Experimentation ; Human immunodeficiency virus ; Human viral diseases ; Humans ; Infectious diseases ; Medical sciences ; Pharmacology. Drug treatments ; pravastatin ; Pravastatin - adverse effects ; Pravastatin - pharmacokinetics ; Pyrroles - adverse effects ; Pyrroles - pharmacokinetics ; Ritonavir - pharmacokinetics ; Saquinavir - pharmacokinetics ; simvastatin ; Simvastatin - adverse effects ; Simvastatin - pharmacokinetics ; Viral diseases ; Viral diseases of the lymphoid tissue and the blood. Aids
ispartofAIDS (London), 2002, Vol.16 (4), p.569-577
rights2002 INIST-CNRS
lds50peer_reviewed
citedbyFETCH-LOGICAL-1420t-667c75cfa0031f558a5cfd054f09a719da200a8fca7483c667e8001433263ff00
citesFETCH-LOGICAL-1420t-667c75cfa0031f558a5cfd054f09a719da200a8fca7483c667e8001433263ff00
links
openurl$$Topenurl_article
thumbnail$$Usyndetics_thumb_exl
backlink
0$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=13546862$$DView record in Pascal Francis
1$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11873000$$D View this record in MEDLINE/PubMed
search
creatorcontrib
0FICHTENBAUM, Carl J
1GERBER, John G
2ROSENKRANZ, Susan L
3SEGAL, Yoninah
4ABERG, Judith A
5BLASCHKE, Terrence
6ALSTON, Beverly
7FANG FANG
8KOSEL, Bradley
9AWEEKA, Francesca
10NIAID AIDS Clinical Trials Group
title
0Pharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047
1AIDS (London)
addtitleAIDS
descriptionLipid lowering therapy is used increasingly in persons with HIV infection in the absence of safety data or information on drug interactions with antiretroviral agents. The primary objectives of this study were to examine the effects of ritonavir (RTV) plus saquinavir soft-gel (SQVsgc) capsules on the pharmacokinetics of pravastatin, simvastatin, and atorvastatin, and the effect of pravastatin on the pharmacokinetics of nelfinavir (NFV) in order to determine clinically important drug-drug interactions. Randomized, open-label study in healthy, HIV seronegative adults at AIDS Clinical Trials Units across the USA. Three groups of subjects (arms 1, 2, and 3) received pravastatin, simvastatin or atorvastatin (40 mg daily each) from days 1-4 and 15-18. In these groups, RTV 400 mg and SQVsgc 400 mg twice daily were given from days 4-18. A fourth group (arm 4) received NFV 1250 mg twice daily from days 1-14 with pravastatin 40 mg daily added from days 15-18. Statin and NFV levels were measured by liquid chromatography/tandem mass spectrometry. Fifty-six subjects completed both pharmacokinetic study days. In arms 1-3, the median estimated area under the curves (AUC)(0-24) for the statins were: pravastatin (arm 1, n = 13), 151 and 75 ng.h/ml on days 4 and 18 (decline of 50% in presence of RTV/SQVsgc), respectively (P = 0.005); simvastatin (arm 2, n = 14), 17 and 548 ng.h/ml on days 4 and 18 (increase of 3059% in the presence of RTV/SQVsgc), respectively (P < 0.001); and total active atorvastatin (arm 3, n = 14), 167 and 289 ng.h/ml on days 4 and 18 (increase of 79% in the presence of RTV/SQVsgc), respectively (P < 0.001). In arm 4, the median estimated AUC(0-8) for NFV (24 319 versus 26 760 ng.h/ml; P = 0.58) and its active M8 metabolite (15 565 versus 14 571 ng.h/m; P = 0.63) were not statistically different from day 14 to day 18 (without or with pravastatin). Simvastatin should be avoided and atorvastatin may be used with caution in persons taking RTV and SQVsgc. Dose adjustment of pravastatin may be necessary with concomitant use of RTV and SQVsgc. Pravastatin does not alter the NFV pharmacokinetics, and thus appears to be safe for concomitant use.
subject
0Adult
1Antibiotics. Antiinfectious agents. Antiparasitic agents
2Anticholesteremic Agents - adverse effects
3Anticholesteremic Agents - pharmacokinetics
4Antiviral agents
5Atorvastatin
6Biological and medical sciences
7Drug Interactions
8Heptanoic Acids - adverse effects
9Heptanoic Acids - pharmacokinetics
10HIV Protease Inhibitors - pharmacokinetics
11HIV Seronegativity
12Human Experimentation
13Human immunodeficiency virus
14Human viral diseases
15Humans
16Infectious diseases
17Medical sciences
18Pharmacology. Drug treatments
19pravastatin
20Pravastatin - adverse effects
21Pravastatin - pharmacokinetics
22Pyrroles - adverse effects
23Pyrroles - pharmacokinetics
24Ritonavir - pharmacokinetics
25Saquinavir - pharmacokinetics
26simvastatin
27Simvastatin - adverse effects
28Simvastatin - pharmacokinetics
29Viral diseases
30Viral diseases of the lymphoid tissue and the blood. Aids
issn
00269-9370
11473-5571
fulltextfalse
rsrctypearticle
creationdate2002
recordtypearticle
recordideNqFkE1v1DAQhi0EokvhLyBf4BYYx3HscEBaraCtVAkkCtdo1hlTQ9YutlPUf4-XXajEBV9G8_qZr5cxLuCVgEG_hvpakNC0h2ig2UvmAVuJTstGKS0eshW0_dAMUsMJe5Lzt0ooMOYxOxHCaFnTFVs-XmPaoY3ffaDiLfehUEJbfAyZb6n8JAr8JsVCmKn-XvutLzFljmHiuWDxlfOBn1984ZlSDPS1arfEb-O81F6U8hu-3lyd8U9lme74WkGnn7JHDudMz47xlH1-_-5qc95cfji72KwvG9G1UJq-11Yr6xBACqeUwZpMoDoHA2oxTFjvR-Ms6s5IW3EyAKKTsu2lcwCn7OWhbz3gx0K5jDufLc0zBopLHoWRrTBCVNAcQJtizonceJP8DtPdKGDcWz7-sXz8a_lvydTS58cZy3ZH033h0eMKvDgCmC3OLmGwPt9zUnW96dvKvf1nB-v3_sZQEvr5_5v8Aj3am1s
startdate2002
enddate2002
creator
0FICHTENBAUM, Carl J
1GERBER, John G
2ROSENKRANZ, Susan L
3SEGAL, Yoninah
4ABERG, Judith A
5BLASCHKE, Terrence
6ALSTON, Beverly
7FANG FANG
8KOSEL, Bradley
9AWEEKA, Francesca
generalLippincott Williams & Wilkins
scope
0IQODW
1CGR
2CUY
3CVF
4ECM
5EIF
6NPM
7AAYXX
8CITATION
97U9
10H94
sort
creationdate2002
titlePharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047
authorFICHTENBAUM, Carl J ; GERBER, John G ; ROSENKRANZ, Susan L ; SEGAL, Yoninah ; ABERG, Judith A ; BLASCHKE, Terrence ; ALSTON, Beverly ; FANG FANG ; KOSEL, Bradley ; AWEEKA, Francesca
facets
frbrtype5
frbrgroupidcdi_FETCH-LOGICAL-1420t-667c75cfa0031f558a5cfd054f09a719da200a8fca7483c667e8001433263ff00
rsrctypearticles
prefilterarticles
languageeng
creationdate2002
topic
0Adult
1Antibiotics. Antiinfectious agents. Antiparasitic agents
2Anticholesteremic Agents - adverse effects
3Anticholesteremic Agents - pharmacokinetics
4Antiviral agents
5Atorvastatin
6Biological and medical sciences
7Drug Interactions
8Heptanoic Acids - adverse effects
9Heptanoic Acids - pharmacokinetics
10HIV Protease Inhibitors - pharmacokinetics
11HIV Seronegativity
12Human Experimentation
13Human immunodeficiency virus
14Human viral diseases
15Humans
16Infectious diseases
17Medical sciences
18Pharmacology. Drug treatments
19pravastatin
20Pravastatin - adverse effects
21Pravastatin - pharmacokinetics
22Pyrroles - adverse effects
23Pyrroles - pharmacokinetics
24Ritonavir - pharmacokinetics
25Saquinavir - pharmacokinetics
26simvastatin
27Simvastatin - adverse effects
28Simvastatin - pharmacokinetics
29Viral diseases
30Viral diseases of the lymphoid tissue and the blood. Aids
toplevelpeer_reviewed
creatorcontrib
0FICHTENBAUM, Carl J
1GERBER, John G
2ROSENKRANZ, Susan L
3SEGAL, Yoninah
4ABERG, Judith A
5BLASCHKE, Terrence
6ALSTON, Beverly
7FANG FANG
8KOSEL, Bradley
9AWEEKA, Francesca
10NIAID AIDS Clinical Trials Group
collection
0Pascal-Francis
1Medline
2MEDLINE
3MEDLINE (Ovid)
4MEDLINE
5MEDLINE
6PubMed
7CrossRef
8Virology and AIDS Abstracts
9AIDS and Cancer Research Abstracts
jtitleAIDS (London)
delivery
delcategoryRemote Search Resource
fulltextno_fulltext
addata
au
0FICHTENBAUM, Carl J
1GERBER, John G
2ROSENKRANZ, Susan L
3SEGAL, Yoninah
4ABERG, Judith A
5BLASCHKE, Terrence
6ALSTON, Beverly
7FANG FANG
8KOSEL, Bradley
9AWEEKA, Francesca
aucorpNIAID AIDS Clinical Trials Group
formatjournal
genrearticle
ristypeJOUR
atitlePharmacokinetic interactions between protease inhibitors and statins in HIV seronegative volunteers: ACTG Study A5047
jtitleAIDS (London)
addtitleAIDS
date2002
risdate2002
volume16
issue4
spage569
epage577
pages569-577
issn0269-9370
eissn1473-5571
abstractLipid lowering therapy is used increasingly in persons with HIV infection in the absence of safety data or information on drug interactions with antiretroviral agents. The primary objectives of this study were to examine the effects of ritonavir (RTV) plus saquinavir soft-gel (SQVsgc) capsules on the pharmacokinetics of pravastatin, simvastatin, and atorvastatin, and the effect of pravastatin on the pharmacokinetics of nelfinavir (NFV) in order to determine clinically important drug-drug interactions. Randomized, open-label study in healthy, HIV seronegative adults at AIDS Clinical Trials Units across the USA. Three groups of subjects (arms 1, 2, and 3) received pravastatin, simvastatin or atorvastatin (40 mg daily each) from days 1-4 and 15-18. In these groups, RTV 400 mg and SQVsgc 400 mg twice daily were given from days 4-18. A fourth group (arm 4) received NFV 1250 mg twice daily from days 1-14 with pravastatin 40 mg daily added from days 15-18. Statin and NFV levels were measured by liquid chromatography/tandem mass spectrometry. Fifty-six subjects completed both pharmacokinetic study days. In arms 1-3, the median estimated area under the curves (AUC)(0-24) for the statins were: pravastatin (arm 1, n = 13), 151 and 75 ng.h/ml on days 4 and 18 (decline of 50% in presence of RTV/SQVsgc), respectively (P = 0.005); simvastatin (arm 2, n = 14), 17 and 548 ng.h/ml on days 4 and 18 (increase of 3059% in the presence of RTV/SQVsgc), respectively (P < 0.001); and total active atorvastatin (arm 3, n = 14), 167 and 289 ng.h/ml on days 4 and 18 (increase of 79% in the presence of RTV/SQVsgc), respectively (P < 0.001). In arm 4, the median estimated AUC(0-8) for NFV (24 319 versus 26 760 ng.h/ml; P = 0.58) and its active M8 metabolite (15 565 versus 14 571 ng.h/m; P = 0.63) were not statistically different from day 14 to day 18 (without or with pravastatin). Simvastatin should be avoided and atorvastatin may be used with caution in persons taking RTV and SQVsgc. Dose adjustment of pravastatin may be necessary with concomitant use of RTV and SQVsgc. Pravastatin does not alter the NFV pharmacokinetics, and thus appears to be safe for concomitant use.
copHagerstown, MD
pubLippincott Williams & Wilkins
pmid11873000
doi10.1097/00002030-200203080-00008