Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents

Objective: To assess pharmacokinetics, safety and efficacy of darunavir/ritonavir (DRV/r) and optimized background regimen in treatment-experienced patients (6-17 years). Design: Forty-eight-week, open-label, two-part, phase II study. Methods: In part I, 44 patients were randomized (1 : 1 ratio) to...

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Autores: Blanche, Stephane, Bologna, Rosa, Cahn, Pedro, Rugina, Sorin, Flynn, Patricia, Fortuny, Claudia, Vis, Peter, Sekar, Vanitha, van Baelen, Ben, Dierynck, Inge, Spinosa-Guzman, Sabrina
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2009
País:España
Institución:Fundació Sant Joan de Déu
Repositorio:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
OAI Identifier:oai:fsjd.fundanetsuite.com:p6029
Acceso en línea:https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6029
Access Level:acceso abierto
Palabra clave:children
darunavir
HIV
safety
treatment-experienced
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spelling Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescentsBlanche, StephaneBologna, RosaCahn, PedroRugina, SorinFlynn, PatriciaFortuny, ClaudiaVis, PeterSekar, Vanithavan Baelen, BenDierynck, IngeSpinosa-Guzman, SabrinachildrendarunavirHIVsafetytreatment-experiencedObjective: To assess pharmacokinetics, safety and efficacy of darunavir/ritonavir (DRV/r) and optimized background regimen in treatment-experienced patients (6-17 years). Design: Forty-eight-week, open-label, two-part, phase II study. Methods: In part I, 44 patients were randomized (1 : 1 ratio) to receive a body weight-adjusted, adult-equivalent dose (group A) or a 20-33% higher DRV/r twice daily (b.i.d.) dose (group B). Pharmacokinetics, safety and efficacy were assessed following 2-week dosing (part I), which determined dosing for part II (evaluated 48-week safety and efficacy). Results: In part I, both groups met the protocol-specified criteria for pharmacokinetics and showed favorable tolerability and efficacy. The following body-weight doses were selected: DRV/r 375/50 mg b.i.d. (20-<30 kg), 450/60 mg b.i.d. (30-<40 kg) and 600/100 mg b.i.d. (>= 40 kg); these gave an AUC(24h), C(0h), and C(max) of 102, 114 and 112%, respectively, versus the corresponding mean adult pharmacokinetic parameter. In part II, 80 patients received DRV/r (median age: 14 years, mean baseline HIV-1 RNA: 4.64 log(10)copies/ml). One patient (1%) discontinued (treatment-unrelated grade 3 anxiety). An abnormal mean baseline triglyceride level was normalized at 48 weeks (P<0.01). At week 48, 65% had at least 1.0 log(10)HIV-1 RNA reduction; 59 and 48% achieved HIV-1 RNA less than 400 and less than 50 copies/ml, respectively (time-to-loss-of-virologic response). Mean age-adjusted weight z-score increased by 0.2 (P=0.003). Conclusion: In treatment-experienced children and adolescents, DRV/r showed comparable exposure to adults with appropriate dose selection, favorable safety and tolerability, improved body weight and significant virologic response. DRV/r is a valuable therapeutic option for this population. (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & WilkinsLIPPINCOTT WILLIAMS & WILKINS2009info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttps://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6029AIDSISSN: 02699370ISSNe: 14735571reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déuinstname:Fundació Sant Joan de DéuInglésinfo:eu-repo/semantics/openAccessoai:fsjd.fundanetsuite.com:p60292026-05-27T12:37:41Z
dc.title.none.fl_str_mv Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents
title Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents
spellingShingle Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents
Blanche, Stephane
children
darunavir
HIV
safety
treatment-experienced
title_short Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents
title_full Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents
title_fullStr Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents
title_full_unstemmed Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents
title_sort Pharmacokinetics, safety and efficacy of darunavir/ritonavir in treatment-experienced children and adolescents
dc.creator.none.fl_str_mv Blanche, Stephane
Bologna, Rosa
Cahn, Pedro
Rugina, Sorin
Flynn, Patricia
Fortuny, Claudia
Vis, Peter
Sekar, Vanitha
van Baelen, Ben
Dierynck, Inge
Spinosa-Guzman, Sabrina
author Blanche, Stephane
author_facet Blanche, Stephane
Bologna, Rosa
Cahn, Pedro
Rugina, Sorin
Flynn, Patricia
Fortuny, Claudia
Vis, Peter
Sekar, Vanitha
van Baelen, Ben
Dierynck, Inge
Spinosa-Guzman, Sabrina
author_role author
author2 Bologna, Rosa
Cahn, Pedro
Rugina, Sorin
Flynn, Patricia
Fortuny, Claudia
Vis, Peter
Sekar, Vanitha
van Baelen, Ben
Dierynck, Inge
Spinosa-Guzman, Sabrina
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv children
darunavir
HIV
safety
treatment-experienced
topic children
darunavir
HIV
safety
treatment-experienced
description Objective: To assess pharmacokinetics, safety and efficacy of darunavir/ritonavir (DRV/r) and optimized background regimen in treatment-experienced patients (6-17 years). Design: Forty-eight-week, open-label, two-part, phase II study. Methods: In part I, 44 patients were randomized (1 : 1 ratio) to receive a body weight-adjusted, adult-equivalent dose (group A) or a 20-33% higher DRV/r twice daily (b.i.d.) dose (group B). Pharmacokinetics, safety and efficacy were assessed following 2-week dosing (part I), which determined dosing for part II (evaluated 48-week safety and efficacy). Results: In part I, both groups met the protocol-specified criteria for pharmacokinetics and showed favorable tolerability and efficacy. The following body-weight doses were selected: DRV/r 375/50 mg b.i.d. (20-<30 kg), 450/60 mg b.i.d. (30-<40 kg) and 600/100 mg b.i.d. (>= 40 kg); these gave an AUC(24h), C(0h), and C(max) of 102, 114 and 112%, respectively, versus the corresponding mean adult pharmacokinetic parameter. In part II, 80 patients received DRV/r (median age: 14 years, mean baseline HIV-1 RNA: 4.64 log(10)copies/ml). One patient (1%) discontinued (treatment-unrelated grade 3 anxiety). An abnormal mean baseline triglyceride level was normalized at 48 weeks (P<0.01). At week 48, 65% had at least 1.0 log(10)HIV-1 RNA reduction; 59 and 48% achieved HIV-1 RNA less than 400 and less than 50 copies/ml, respectively (time-to-loss-of-virologic response). Mean age-adjusted weight z-score increased by 0.2 (P=0.003). Conclusion: In treatment-experienced children and adolescents, DRV/r showed comparable exposure to adults with appropriate dose selection, favorable safety and tolerability, improved body weight and significant virologic response. DRV/r is a valuable therapeutic option for this population. (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins
publishDate 2009
dc.date.none.fl_str_mv 2009
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6029
url https://fsjd.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=6029
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv LIPPINCOTT WILLIAMS & WILKINS
publisher.none.fl_str_mv LIPPINCOTT WILLIAMS & WILKINS
dc.source.none.fl_str_mv AIDS
ISSN: 02699370
ISSNe: 14735571
reponame:r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
instname:Fundació Sant Joan de Déu
instname_str Fundació Sant Joan de Déu
reponame_str r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
collection r-FSJD. Repositorio Institucional de Producción Científica de la Fundació Sant Joan de Déu
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812429

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