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Titolo:
Pharmacokinetics and resistance mutations affect virologic response to ritonavir/saquinavir-containing regimens
Autore:
Pellegrin, I; Breilh, D; Birac, V; Deneyrolles, M; Mercie, P; Trylesinski, A; Neau, D; Saux, MC; Fleury, HJA; Pellegrin, JL;
Indirizzi:
Bordeaux Univ Hosp, Dept Virol, Bordeaux, France Bordeaux Univ Hosp Bordeaux France v Hosp, Dept Virol, Bordeaux, France Bordeaux Univ Hosp, Dept Pharm, Bordeaux, France Bordeaux Univ Hosp Bordeaux France v Hosp, Dept Pharm, Bordeaux, France Bordeaux Univ Hosp, Dept Internal Med & Infect Dis, Bordeaux, France Bordeaux Univ Hosp Bordeaux France l Med & Infect Dis, Bordeaux, France Roche Pharmaceut, Paris, France Roche Pharmaceut Paris FranceRoche Pharmaceut, Paris, France
Titolo Testata:
THERAPEUTIC DRUG MONITORING
fascicolo: 4, volume: 23, anno: 2001,
pagine: 332 - 340
SICI:
0163-4356(200108)23:4<332:PARMAV>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
HIV-INFECTED PATIENTS; IMMUNODEFICIENCY-VIRUS PROTEASE; SAQUINAVIR-CONTAINING REGIMEN; PLASMA DRUG CONCENTRATIONS; RITONAVIR PLUS SAQUINAVIR; POPULATION PHARMACOKINETICS; COMBINATION THERAPY; INHIBITOR THERAPY; ZIDOVUDINE; DIDANOSINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
30
Recensione:
Indirizzi per estratti:
Indirizzo: Pellegrin, I Hop Pellegrin, Virol Lab, Pl Amelie Raba Leon, F-33076 Bordeaux, France Hop Pellegrin Pl Amelie Raba Leon Bordeaux France F-33076 ce
Citazione:
I. Pellegrin et al., "Pharmacokinetics and resistance mutations affect virologic response to ritonavir/saquinavir-containing regimens", THER DRUG M, 23(4), 2001, pp. 332-340

Abstract

The authors assessed the impact of protease and reverse transcription (RT)mutations and individual pharmacokinetic parameters on virologic response to a four-drug regimen including ritonavir/saquinavir. Treatment was given at the start of the study (M0) to 22 HIV-1 protease inhibitor-naive or pretreated patients. Protease and RT genes were sequenced at M0, at the time ofvirologic failure, or at the end of the follow-up. Plasma ritonavir and saquinavir peak C-max, C-min, and area under the curve (AUC) were determined based on samples taken 0, 1, 2, 3, 4, 6, 8, and 12 hours after administration. HIV-1 RNA decreased to less than 50 copies/mL in 11 patients (group 1). At M0, five of them had no RT mutation and 10 had three or fewer secondaryprotease mutations with no new mutation during follow-up. Ritonavir and saquinavir pharmacokinetics showed wide interindividual variability. Treatment failed in 11 patients (group 2): 9 had three to eight protease mutations and a mean of 5.8 RT mutations at M0, with emergence of new mutations during follow-up. Pharmacokinetics was similar to those of group 1. The other two patients with virologic failure showed no baseline primary mutation but were the only patients with insufficient saquinavir and ritonavir AUC. The authors showed the complementarity between drug-resistance genotype and individual pharmacokinetics and the potential utility of AUC and C-max to manage treatment.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 23:54:36