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Titolo:
A phase I trial of the pharmacokinetics, toxicity, and activity of KNI-272, an inhibitor of HIV-1 protease, in patients with AIDS or symptomatic HIV infection
Autore:
Humphrey, RW; Wyvill, KM; Nguyen, BY; Shay, LE; Kohler, DR; Steinberg, SM; Ueno, T; Fukasawa, T; Shintani, M; Hayashi, H; Mitsuya, H; Yarchoan, R;
Indirizzi:
NCI,AHIV & AIDS Malignancy Branch, Div Clin Sci, NIH, Bethesda, MD 20892 US NCI Bethesda MD USA 20892 ranch, Div Clin Sci, NIH, Bethesda, MD 20892 US NCI, Biostat & Data Management Sect, Div Clin Sci, Bethesda, MD 20892 USA NCI Bethesda MD USA 20892 ment Sect, Div Clin Sci, Bethesda, MD 20892 USA NCI, Med Branch, Div Clin Sci, Bethesda, MD 20892 USA NCI Bethesda MD USA20892 ed Branch, Div Clin Sci, Bethesda, MD 20892 USA NIH, Warren G Magnuson Clin Ctr, Dept Pharm, Bethesda, MD 20892 USA NIH Bethesda MD USA 20892 on Clin Ctr, Dept Pharm, Bethesda, MD 20892 USA Japan Energy Corp, Tokyo, Japan Japan Energy Corp Tokyo JapanJapan Energy Corp, Tokyo, Japan
Titolo Testata:
ANTIVIRAL RESEARCH
fascicolo: 1, volume: 41, anno: 1999,
pagine: 21 - 33
SICI:
0166-3542(199902)41:1<21:APITOT>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNODEFICIENCY-VIRUS PROTEASE; RATIONAL DESIGN; DRUG-RESISTANCE; RITONAVIR; PLASMA; ALLOPHENYLNORSTATINE; SAQUINAVIR; INVITRO; I/II; RATS;
Keywords:
KNI-272; HIV-1 protease; AIDS; HIV; protease inhibitor;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
36
Recensione:
Indirizzi per estratti:
Indirizzo: Yarchoan, R NCI,thesda,AIDS Malignancy Branch, Div Clin Sci, NIH, Bldg 10,Rm 12N226, Be NCI Bldg 10,Rm 12N226 Bethesda MD USA 20892 g 10,Rm 12N226, Be
Citazione:
R.W. Humphrey et al., "A phase I trial of the pharmacokinetics, toxicity, and activity of KNI-272, an inhibitor of HIV-1 protease, in patients with AIDS or symptomatic HIV infection", ANTIVIR RES, 41(1), 1999, pp. 21-33

Abstract

The pharmacokinetics, toxicity, and activity of KNI-272, a transition state inhibitor of HIV-1 protease, was assessed in a phase 1 trial. After an initial phase in which the pharmacokinetics were assessed, 37 patients with AIDS or symptomatic HIV infection and 100-400 CD4 cells/mm(3) were entered in an escalating dose study. KNI-272 was administered four times daily for up to 12 weeks. Oral bioavailability ranged from 22 to 55% and was not appreciably different in the fasting and post-prandial state. The dose limiting toxicity was hepatic transaminase elevation; this could be reduced by escalating the dose over 4 weeks. When administered this way, the maximum tolerated oral dose was 40 mg:kg per day. At the highest two tolerated doses (26.4 and 40 mg/kg per day), there was some evidence of an anti-HIV effect withmedian decreases of 0.2-0.3 log(10) copies:ml plasma HIV RNA; these decreases persisted through 7-8 weeks of treatment. There was an upward trend in the CD4 count at the 40 mg/kg per day dose but not at other doses. Additional studies focused on approaches to improve the therapeutic index of KNI-272 may be warranted. (C) 1999 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 02:09:52